We Pioneered a Technology to Save Millions of Poor Children, But a Worldwide Smear Campaign Has Blocked It
On left, a picture of white rice next to Golden Rice, and on right, a girl who lost one eye due to vitamin A deficiency.
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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Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman