Biologists decode oxygen sensors in cells to win Nobel Prize in Medicine

William Kaelin, Peter Ratcliffe and Gregg Semenza have together worked out how genes respond when oxygen is depleted.Credit: Ill. Niklas Elmedhed/Nobel Media

Three scientists - cancer researcher William Kaelin at the Dana-Farber Cancer Institute in Boston, Massachusetts; physician-scientist Peter Ratcliffe at the University of Oxford, UK, and the Francis Crick Institute in London; and geneticist Gregg Semenza at Johns Hopkins University in Baltimore, Maryland have won the 2019 Nobel Prize in Physiology or Medicine for describing how cells sense and respond to oxygen by switching genes on and off. 

The team also won the Albert Lasker Basic Medical Research Award in 2016.

 This discovery has been key in understanding human diseases such as cancer and anaemia. Among the applications of their discovery is a better understanding of how the body reacts when oxygen levels drop owing to exercise or stroke, and efforts to manipulate the response to slow the growth of oxygen-hungry cancer tumours.

Their work has helped researchers to understand how the body adapts to low oxygen levels by, for example, cranking out red blood cells and growing new blood vessels.

“This is a fundamental discovery that they’ve contributed to” says Celeste Simon, a cancer biologist at the University of Pennsylvania in Philadelphia. “All organisms need oxygen, so it’s really important.

“The field really coalesced around this discovery, which was dependent on each one of their findings,” says Randall Johnson, a physiologist at the University of Cambridge, UK, and the Karolinska Institute in Stockholm, and a member of the Nobel Assembly. “This really was a three-legged stool.”

In work conducted in the 1990s, the scientists discovered the molecular processes that cells go through to respond to oxygen levels in the body. They found that central to this is a mechanism involving proteins called HIF and VHL.

Meanwhile, Kaelin showed that a gene called VHL also seemed to be involved in how cells respond to oxygen, through studying a genetic syndrome called von Hippel-Lindau’s disease; families with the disease carry mutations in VHL and the condition raises the risk of certain cancers. Semenza and Ratcliffe studied the regulation of a hormone called erythropoietin (EPO), which is crucial for stimulating the production of red blood cells in response to low levels of oxygen. Semenza and his team identified a pair of genes that encode the two proteins that form a protein complex called hypoxia-inducible factor (HIF), which work together to turn on certain genes and boost erythropoietin production when oxygen is low.

Ratcliffe and his team later found that the protein expressed by the VHL gene interacts with one of the components of HIF, turning off responses to low-oxygen conditions by marking the HIF component for destruction once oxygen levels rise.

And in 2001, teams led by Kaelin and Ratcliffe both showed that, as part of this process, a chemical modification to the VHL protein, called prolyl hydroxylation, allows cells to respond to oxygen levels incredibly rapidly. When oxygen is present, the modified form of VHL can bind to HIF, which leads to its breakdown. But this modification is blocked when cells are oxygen-starved, kick-starting the activity of HIF.

As a result, cells can react to low oxygen levels by simply blocking the breakdown of HIF, notes Mark Dewhirst, a cancer biologist at Duke University in Durham, North Carolina. “The cell can respond in minutes.”

The work has led researchers to develop drugs that target oxygen-sensing processes, including for cancer. Drugs that prevent VHL from binding to HIF and causing its degradation, called prolyl hydroxylase inhibitors, are also being investigated as treatments for anaemia and renal failure. Chinese regulators approved the first of these drugs in 2018.

Woman's cornea repaired with ‘reprogrammed’ stem cells

A 40-year-old Japanese woman is the first person in the world to have her cornea repaired using reprogrammed stem cells, according to Nature.

Ophthalmologist Kohji Nishida from Osaka University, Japan, said the woman has a disease in which the stem cells that repair the cornea, a transparent layer that covers and protects the eye, are lost. The condition makes vision blurry and can lead to blindness.

To treat the woman, Nishida says his team created sheets of corneal cells from induced Pluripotent Stem (iPS) cells. 

These are made by reprogramming adult skin cells from a donor into an embryonic-like state from which they can transform into other cell types, such as corneal cells.

Nishida said that the woman’s cornea remained clear and her vision had improved since the transplant a month ago.

Currently, people with damaged or diseased corneas are generally treated using tissue from donors who have died, but there is a long waiting list for such tissue in Japan.

Japan has been ahead of the curve in approving the clinical use of iPS cells, which were discovered by stem-cell biologist Shinya Yamanaka at Kyoto University, who won a Nobel prize for the work. Japanese physicians have also used iPS cells to treat spinal cord injury and Parkinson's disease among others.

Lagos plans 1m birth registrations in 2019

The Lagos State government has stepped up efforts to register children from birth even as it has been mandated by the National Population Commission (NPopC) to register 1 million children by the end of the year.

With a total of 231,584 registrations comprising 117,586 boys and 113,998  girls, Lagos had the 2^nd highest number of birth registrations in the country in 2018 after Borno State.

The Lagos State 2019 report shows that the worst-performing Local Government Areas (LGAs) are Epe with 28,817 registrations, Lagos Island 28,579 registrations, and Ibeju- Lekki with 18,346 registrations.

In 2018, the worst-performing LGAs were Ajeromi/Ifelodun with 34 percent, Lagos mainland with 36 percent and Mushin with 41 percent birth registration.

In the views of UNICEF Child Protection Specialist, Mrs. Sharon Oladiji, “Birth registration is the first step towards recognizing a child’s inalienable right as a human being, but in Lagos state, this is failing to meet their right to an identity, name and nationality.”

Oladiji who spoke during a two-day media workshop organized by the National Orientation Agency (NOA) in collaboration with UNICEF, on the need to scale up birth registration in Lagos State decried the threat to the rights of over 1.4 million children in the state, even as she called for expansion of birth registration services in all LGAs with prioritization of interventions to accelerate progress, especially amongst the poor in rural areas and among socially disadvantaged groups.

“ When a child is not registered, there is no official record of his/her full names and that child will not have access to basic services,” said the Head of Department, Vital Registration Department, National Population Commission, NPoPC Lagos State, Mr. Nwannukwu Ikechukwu.

He said to scale up the number of registered births in Lagos, the Commission plans to create an additional 26 centres across the state.

Nwannukwu blamed the low birth registration rate in the State to myriads of challenges including lack of suitable offices for comptrollers and registrars; touting of birth and death certificate; the unhealthy rivalry between Lagos state council staff and NPoPC registrars among others.

The HOD, however, emphasized the importance of improved service delivery, identification of barriers and bottlenecks, forging community-based approaches and encouraging innovation as the solution to the identified problems of weak birth registration system.

He urged the State government to employ more ad hoc registrars, to enable the commission to cover more areas, especially in hard to reach communities within the state.

On his part, Lagos State Director, National Orientation Agency, NOA, Mr. Waheed Ishola, who noted that the media was critical in the scaling up of birth registration, appealed to media practitioners to buy into the programme and help create awareness on the project.

Provisions in the current legislation for birth registration make it mandatory. The Federal Government’s decree No. 69 of 1992 on vital registration states that registration shall be carried out free of charge, within a period of 60 days from the date of birth.

Birth registration is the continuous, permanent, compulsory and universal recording of the occurrence and characteristics of birth. The exercise is free nationwide for children aged 0-17 years.

Information from RapidSMS, a data tracking tool that collects and collates real-time information using Short Messaging System (SMS),  in 2018, 175,912 children under one year were registered comprising 86,497 girls and 89,415 boys while 308,529 Under fives comprising 155,031 girls and 253,497 boys were registered.

For 2017, the State registered 211,312 children under age one, 103,801 girls and 307,509 boys, under five 338,195, while for girls 165,611 and 072, 585 for boys.

In 2016, a total of 197,814 children were registered (101,157 boys and 96,657 girls). Under fives registered were 321,228 (157,081 girls and 64,148 boys), while

In 2015, Lagos State registered 176,533 children under the age of one, comprising 87,693 girls and 88,840 boys while for the Under fives, 236, 592 children were registered made up of 117,041 girls and 119,551 boys.

Medical abortion and matters arising

AS soon as she discovered she was pregnant, Comfort, a young Nigerian woman immediately made up her mind she was not keeping it. As events later showed, the unnamed housewife had given birth thrice in the past but for reasons best known to her, she put her foot down and insisted the fourth pregnancy had to go.

“I was a full-time housewife and my husband had just lost his job,” she narrated. “We were literarily struggling to put food on the table and pay all the bills. Survival was difficult. I wasn’t on any family planning method and we already had three children spaced less than two years apart and the eldest was barely 6, so another pregnancy was simply out of the question.”

“I did not even tell my husband I was pregnant. I knew if I did, he would try to convince me to keep it. For me though, the decision was made as soon as I heard that I was pregnant and I just went all out and terminated it on my own.”

But Comfort did not immediately makeup her mind how the unwanted pregnancy as to be terminated. Over the next few weeks, she pondered over the issue and finally settled for an unsafe abortion through the use of certain "pills" and "tablets" to initiate a crude medical abortion of the growing fetus.

“I bought the pills and some other recommended medicines that I was told were efficient in inducing abortion. I took them at home early one morning and started bleeding soon afterward.

“The bleeding became so much and I felt a bit of pain, but by the evening of the next day, everything had subsided. My husband did not even suspect anything but I later told him everything a few months afterward.

“He was very surprised and rather angry with me but appealed that I should never to try such a thing again. I promised and I am now on a reliable contraceptive.”

The home is important in the reproductive health story of women in Nigeria. Women get pregnant at home, give birth at home and often induce abortion at home.

Medical abortion actually brings access to safe abortion closer home. All over the country, all classes, women with unwanted pregnancies seek access to safe termination processes across the city women can easily purchase a wide range of drugs without a prescription to bring on their wayward periods.

Like Comfort, millions of Nigerian women experience unwanted pregnancies and resort to unsafe termination with the associated health. Experts say one of the reasons Nigerian women often turn to abortion is to avoid unwanted births.

“The provision of family planning counseling and information could substantially reduce the incidence of unwanted pregnancy and induced abortion in Nigeria,” said Prof Adetokunbo Fabamwo, a Consultant Gynaecologist and the Chief Medical Director, Lagos State University Teaching Hospital, Ikeja, Lagos.

Among  other factors are the fear of isolation and rejection, employment policies, ignorance, completed family, too young or too old.

 In the views of Ms. Sybil Nmezi of the Generation Initiative for Women and Youth Network (GIWYN) millions of women and girls finding themselves with an unintended pregnancy becomes a moment of decision.

Nmezi, who spoke about how barriers to reproductive health care and services affect women’s lives, said the law on abortion in Nigeria was too restrictive and should be reviewed.
  “For some, it is simple and straight forward, for others, it is difficult and complex,” she asserted.

In a study conducted by the Guttmacher Institute, almost a third of the women said they had undergone at least one unwanted pregnancy. About half of them admitted having attempted to end their last unwanted pregnancy.

Speakers at the forum agreed that at least every other woman who seeks an abortion does so because they are not married, are too young or are still in school. Of the women not practicing contraception when they had the unwanted pregnancy, a number are unaware of family planning, and about 1 in 5 either have no access to contraceptive services, or the services are too expensive or they’re afraid of side effects.

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Africa adopts strategic plan to reduce malnutrition

A strategic plan to reduce the double burden of malnutrition in the African Region was recently adopted at the 69th Regional Committee meeting of the World Health Organization (WHO) for the African Region.

 The Regional Committee is the governing mechanism involving health ministers from all 47 Member States of the WHO African Region.

WHO Regional Director for Africa, Dr Matshidiso Moeti, said the plan outlines the urgent and accelerated action to take to meet the goal of ending hunger and all forms of malnutrition by 2030.

“The WHO Secretariat will be developing and implementing a resource mobilization plan, supporting research collaborations and mounting high-level advocacy for increased investment to reach 90% coverage of the 10 highest-impact nutrition interventions that must be taken to meet the malnutrition challenges in our region,” Moeti said.

The double burden of malnutrition is particularly prevalent in countries undergoing “nutrition transformation” in which undernutrition and overweight or obesity coexist, often because of the increasing consumption of cheap, processed foods that are high in energy, fat and salt content but low in nutrient quality.

This diet, which is common in Africa, fails to address chronic undernutrition and micronutrient deficiencies and contributes to increased obesity and diet-related non-communicable diseases.

The the strategic plan aims to strengthen evidence-based policies and national capacity and contains clear targets to be achieved by 2025. Priority interventions include reinforcing legislation and food safety standards, using fiscal measures to incentivize healthy food choices and integrating essential nutrition actions in health service delivery platforms.

The number of undernourished people in sub-Saharan Africa rose from 181 million in 2010 to almost 222 million in 2016. Among children, although the prevalence of stunting decreased from 38.3% in 2000 to 30.3% in 2017, the numbers affected increased from 50.6 million to 58.7 million due to population growth. The rate of wasting in 2017 was 7.1% or 13.8 million children, of whom 4 million were severely wasted.

 Overweight rates are also increasing. The number of children younger than 5 years who are overweight increased from 6.6 million in 2000 to 9.7 million in 2017. For children aged 5–19 years, obesity rates doubled between 2006 and 2016, while for adults, overweight and obesity increased from 28.4% in 2000 to 41.7% in 2016.

UNICEF seeks $70m to provide humanitarian assistance to 900,000 children in Venezuela

UNICEF is appealing for more than US$70 million to provide life-saving humanitarian assistance to 900,000 children across Venezuela through the end of the year. New funding in the coming weeks is essential for UNICEF and its partners to meet the critical humanitarian needs of children and families inside the country.

“Some 3.2 million children in Venezuela need humanitarian aid as conditions across the country continue to deteriorate,” said UNICEF Executive Director Henrietta Fore. 

“We are ramping up our work to help children and families who are struggling against food shortages and limited access to essential services like healthcare, safe water and education.”

At least 4.3 million people across Venezuela do not have access to safe drinking water; vaccine-preventable diseases including measles and diphtheria have re-emerged, while yellow fever and malaria are on the rise. An estimated 1.3 million children and adolescents need protection services, while over 1 million children are out of school.

In line with 2019 Humanitarian Response Plan (HRP) for Venezuela launched by the United Nations and its partners, UNICEF’s priorities for the remainder of the year include: Providing 800,000 people with access to safe drinking water; Continuing to rehabilitate the vaccine cold chain; Vaccinating more than 1,200,000 children under 5 years against measles and ensuring treatment for 7,000 children under 5 years suffering from severe or moderate malnutrition.

Others include distributing education materials to 680,000 children aged 4-18 years; reaching 216,000 children with psychosocial and protection support; and providing over 170,000 pregnant women and newborn babies with health assistance.

These efforts build on UNICEF’s existing programmatic reach which has increased steadily over the past year to meet the growing needs of the most vulnerable children. Since 2018, UNICEF has shipped nearly 200 tons of basic health, nutrition, education, water, and sanitation relief supplies to Venezuela.

Ebola spreads in DR Congo as insecurity persists

CONGOLESE authorities have confirmed a new case of Ebola in the remote, militia-controlled province of Walikale, hundreds of kilometres from previous cases near the border with Uganda and Rwanda. 

Pinga, where the case was reported, is 150 km north-west of Goma, a town affected by the Ebola epidemic and further from the epidemic epicentre in Butembo and Beni. 

The health ministry confirmed the third case in South Kivu region, more than 700 km south of the first case.

Persistent insecurity and unrest are hampering the response in Beni. 

On 19 August 2019, a protest took place in Beni, Butembo and Oicha in response to recent attacks by armed groups on civilians causing temporary suspension of Ebola response activities. 

Operations resumed on 20 August 2019, with extra caution. The suspension of Ebola response activities often results in an increase in case numbers and in cases spreading to new areas in the following weeks.

In the past week, 57 new confirmed Ebola virus disease cases with an additional 46 deaths were reported from 18 health zones in three affected provinces. 

In the 21 days from 29 July through 18 August 2019, 65 health areas in 18 health zones reported new cases, representing 10 percent of the 665 health areas in North Kivu, South Kivu and Ituri provinces. During this period, a total of 215 confirmed cases were reported, with the majority coming from the health zones of Beni.

Cases  detected in two new health zones this past week include Mwenga Health Zone in South Kivu and Pinga Health Zone in North Kivu. In Mwenga, three confirmed cases have been reported thus far after two individuals (mother and child) had contact with a confirmed case in Beni before travelling south. 

The third confirmed case was a co-patient in a community health facility where the first cases initially sought care. In Pinga, one confirmed case has been reported and investigations are ongoing to identify epidemiological links between this individual and outbreak-affected areas. Rapid response teams were quickly deployed to scale up surveillance and response operations in both areas.