Victor Ambros, Gary Ruvkun Win Nobel Prize in Medicine for Discovery of MicroRNA

The discovery of microRNA as “a tiny molecule that has opened a new field in gene regulation,” the Nobel committee said.

American scientists Victor Ambros and Gary Ruvkun have been jointly awarded the Nobel Prize in medicine or physiology for their shared discovery of microRNA and the role it plays in post-transcriptional gene regulation.

The pair’s work to identify the existence and function of microRNA (miRNA) within the body was honoured with the 115th awarding of the medicine prize, which was announced by the Nobel Assembly at the Karolinska Institute in Sweden on Monday morning.

The work was originally started by Ambros at his lab at Harvard University, with Ruvkun performing similar research in his own position at Massachusetts General Hospital.

Why is the discovery of microRNA so important? 

In elaborating on the pair’s work, Nobel Committee vice chair Professor Olle Kämpe described the discovery of microRNA as “a tiny molecule that has opened a new field in gene regulation.”

Though the pair worked in separate labs, their joint research focus led to them combining their resources to expand knowledge of miRNA and its role.

“The seminal discovery of microRNA has introduced a new and unexpected mechanism of gene regulation,” said Kämpe. “MicroRNAs are important for our understanding of embryological development, normal cell physiology and diseases such as cancer. As an example, tumors often perturb microRNA networks to grow.”

Two more science prizes will be awarded this week, with the physics laureate to be revealed on Tuesday and chemistry prize on Wednesday.

This article was originally published on DW.

Kashmir’s Hepatitis-A Scare Is Defined by Inadequate Attention and a Fatal Belief in Faith Healers

Surveillance by trained doctors and good hygiene are both missing in Turka Tachloo, a village in Kulgam where Hepatitis-A has led to the deaths of two children. Then, there is lack of faith in medicine.

Turka Tachloo (Kulgam, J&K): Eight-year-old Afaan Altaf first lost his appetite. Then kindergarten student’s face and eyes started to pale. Within two days, he began to vomit.

The Altafs live in the Turka Tachloo village of south Kashmir’s Kulgam district and were worried about Afaan.

In early December, Afaan’s father Mohammad Altaf – a farmer by profession – decided to visit the Maternity and Child Care hospital in Anantnag town.

“But the doctors there couldn’t make him better. They said that it was up to god, so I thought why not settle the matter with God myself. On the next morning, I took him to Srinagar,” said Altaf, a farmer, who has another boy who is 18 months old.

Official records show that Afaan had tested positive for Hepatitis-A on December 3 following an outbreak of the viral infection in Turka Tachloo. The village comprises about 240 households, most of which are poor and depend on agriculture. It is located 54 kilometres from Srinagar.

A tightly woven cluster of new, modest houses springing up between old structures, the village, whose boundaries seems to have expanded in recent years, is surrounded by expansive paddy fields. Some of the villagers own some of the paddy land, but most of them don’t, and work as labourers. Vishow, a major tributary of Jhelum, forms the village’s northwestern boundary, providing drinking water and also irrigating its paddy fields.

Turka Tachloo is an agricultural village in south Kashmir’s Kulgam district. Photo: Jehangir Ali

A local official said that poor sanitation and lack of hygiene in the village, where nearly half of the population is illiterate, may have contributed to the hepatitis outbreak. According to doctors, the water-borne infection is transmitted through faecal-oral route and the virus can survive for months in favourable conditions.

Locals in Turka Tachloo, however, blamed the administration for negligence which allowed the infected water to reach the village, even though the chlorination process followed by the government’s water filtration plants can’t kill the hepatitis-A virus.

“The condition is so bad that on some days, filthy water comes out of taps. Our elders raised the issue with officials but no one paid any attention,” said Mubashir Maqsood, an engineering graduate from the village.

“Sometimes the tap water is so dirty that you can’t see through it. After collecting it in a container, I keep it aside for some time so that impurities can settle down. What alternatives do we have?,” a woman, who didn’t want to be identified, chipped in.

Government action

The government of India rolled out ‘Drinking water quality testing, monitoring and surveillance framework and guidelines’ in March last year under which a network of ‘National Accreditation Board for Testing and Calibration Laboratories’ (NABL) accredited labs were to be set up in every state, district and block over the next year.

The Union government also set aside two% of its Rs 3.6-lakh-crore Jal Jeevan budget for monitoring water quality across the country.

But the ground situation in J&K paints a dismal picture.

Also read: Kashmir Authorities Restrain Medical Staff From Talking to Media Even as Covid Cases Surge

While the Union Territory has 98 testing laboratories, only three are accredited by NABL, according to the Union government’s Jal Jeevan Mission, implying that the other labs are not equipped to certify the quality of drinking water and raising questions over the credibility of official water testing mechanisms.

A senior official in J&K administration said that Jal Shakti and Health departments run several testing centres across J&K. Shaleen Kabra, commissioner secretary of Jal Shakti, the nodal department for implementing the national framework in J&K, didn’t respond to queries from The Wire about the progress on NABL-accredited labs and the administration’s water testing protocol.

On the ground, after a flurry of visits by top district health and civil officials, the administration has deployed special teams of doctors, local healthcare workers and volunteers to carry door-to-door surveys in Turka Tachloo for screening the population. Four more positive cases have been reported.

Dr Mushtaq Ahmad Rather, Director Health Services (Kashmir) told The Wire that 1,444 persons including children have been screened since the outbreak and more than 300 blood samples have been tested. “From the last two days, there are no positive cases,” Dr Rather said, adding that most patients are students of a village school.

Dr Rather said that the administration is organising awareness campaigns involving community elders and religious activists of the village to encourage people to use boiled water for drinking and cooking purposes. “We are keeping a close eye on the situation,” he said.

Ground realities 

But the government’s initiatives don’t seem to be translating into action on ground. While the infection is water-borne, baby diapers soiled by faecal matter remain strewn along with plastic bags filled with garbage and uneaten food items on the banks of Vishaw, which supplies drinking water to Turka Tachloo.

The banks of Vishow river, which provides drinking water to the village, strewn with soiled diapers and other garbage. Photo: Jehangir Ali

“The villagers continue to use the river as a garbage dumping site, putting themselves and others at risk,” said a health department official, who is not authorised to speak with the media. The local administration has lifted three water samples from the village for testing. While one sample has returned negative, the result of the other two are awaited.

“It is the duty of the government to provide us with pure water. If the water is infected, doesn’t it mean the government is poisoning us? Is the government not accountable to people?” Muzaffar Rehman, a villager, asked.

Anguished by his son’s condition, Altaf who is mentioned at the beginning of this report, fled the hospital in Anantnag against the advice of doctors earlier this month and sought treatment from a traditional faith healer in Srinagar’s Dhara village, a popular address in Kashmir for newborns with severe jaundice and even adult patients with liver dysfunction.

The village is nestled in the foothills of Srinagar’s Zabarwan mountain range. A faith healer there is known to put his patients on a dose of herbal medicines and a lot of prayers. Afaan was one of these patients.

“His condition improved. The level (of bilirubin) went down from 26 to 24 within a day,” Altaf recalled outside his rundown home. The normal ‘total bilirubin’ level for under-18 males is 1 mg/dL.

On the night of December 9, Altaf’s belief in faith healers shattered when Afaan’s condition deteriorated. During an episode of seizure, a condition associated with hepatic encephalopathy, a brain disorder caused by liver failure, he bit his own tongue, cutting and lacerating it badly.

Shocked by the turn of events, he again rushed his son to Anantnag hospital. Doctors there, referred him to Srinagar’s super-speciality ‘Sher-e-Kashmir Institute of Medical Sciences’. The kindergarten student was later admitted to the Children’s Hospital in Srinagar on December 9. The next evening, Afaan’s condition deteriorated further and he slipped into a coma.

“The child had developed encephalitis. He was put on life support but we could not save him,” Dr Rather told The Wire.

Panic and skepticism

Afaan was the second child from Turka Tachloo village who fell prey to the viral infection. On December 7, two days before he was admitted at the children’s hospital, four-year-old Maira Gulzar, daughter of Gulzar Ahmad, a private cab driver, also passed away due to liver dysfunction due to Hepatitis-A infection.

Father of Maira Gulzar showing her photo. The three-year-old girl was second victim of the viral outbreak. Photo: Jehangir Ali

The death of two minors has triggered panic in the village and the deep-rooted belief in faith healers has also taken a hit.

“Had he not fled the hospital, his son could have been alive,” said a villager, wishing not to be named.

More villagers, including women, are turning up at the only health centre to get themselves checked by a team of three doctors who are monitoring the situation with the help of healthcare workers and local volunteers. “I have an ache in the stomach. I want to get tested,” a young woman said to a visiting doctor who counselled her on the hepatitis outbreak, urging her to watch out for symptoms in her family.

Altaf seems to be reconciling with his son’s sudden demise – “it was god’s will and we couldn’t have changed it” – but is discomfited by the mention of the faith healer. “It won’t bring back my son,” he said.

Altaf Ahmad, father of Afaan Altaf, one of the two minors who died in the outbreak, in a tent for mourners outside his house. Photo: Jehangir Ali

Dr Tariq Qureshi, who heads the childcare hospital in Anantnag, said that Afaan’s life could have been saved if his father had not gone against the advice of doctors and continued the treatment.

“It is unfortunate, but many people in Kashmir continue to believe in faith healers. Even the well-educated ones believe in these practices,” he said.

Initial monitoring needed, says expert; others call for trained doctors

Dr Salim Khan, who heads the Social and Preventive Medicine department at Srinagar’s SHMS hospital said that a patient infected by hepatitis A presents with symptoms of body aches, loss of appetite and abdominal pain which correlate with viral infection symptoms.

“Initially a patient doesn’t present with jaundice symptoms and the bilirubin levels are also not raised at this time. People usually neglect these symptoms. It is a self-limiting disease which is treated symptomatically and most of the patients recover on their own. But if the disease progresses, jaundice sets in and in children it can also affect the brain leading to viral encephalitis,” he told The Wire.

He said that the patients need to be monitored by doctors and parents constantly, “More than doctors, it is surveillance and good hygiene which can limit the spread of the disease.”

A ‘Health and Wellness Centre’ has been set up under the National Health Policy of 2017 in Turka Tachloo led by a community health officer and a small team of health workers to “address communicable and non-communicable diseases and services for elderly and palliative care.”

The health centre run by the government in Turka Tachloo village. Photo: Jehangir Ali

A senior health department official in J&K, who didn’t want to be named, said that the health officers often confuse the symptoms of hepatitis with viral infection.

“If trained doctors are posted at the wellness centres instead of health officers, who have a limited scope of practice, such outbreaks could be prevented in future. Also, the water testing mechanism used across the country isn’t so advanced to test the presence of viruses such as hepatitis-A, putting people at risk of catching water-borne viral diseases,” he said.

Ramdev ‘Withdraws’ Statement on Allopathic Medicines After Criticism, Minister’s Letter

The Union health minister’s letter to the yoga guru came after the IMA demanded the Centre to take strict action.

New Delhi: Feeling pressure from the Union health minister as well as the Indian Medical Association (IMA), yoga guru and businessman Ramdev on Sunday night said he was “withdrawing” his statements criticising allopathic medicines. Ramdev had earlier reportedly said that more people are dying due to modern medicines during the COVID-19 crisis than the virus itself.

Union health minister Harsh Vardhan on Sunday called Ramdev’s statement on allopathic medicines “extremely unfortunate” and asked him to withdraw it, a day after the IMA demanded that the Centre should take strict action against him for “misleading people by making unlearned” comments and describing modern medicine as “stupid science”.

Citing a video circulating on social media, the IMA on Saturday had said Ramdev has claimed that allopathy is a “stupid science” and medicines such as remdesivir, faviflu, and other drugs approved by the Drugs Controller General of India have failed to treat COVID-19 patients.

The doctors’ body also quoted Ramdev as saying that “lakhs of patients have died after taking allopathic medicines”.

These remarks were denied as misconstrued by the Haridwar-based Patanjali Yogpeeth Trust, headed by Ramdev. Patanjali too has been criticised during this crisis for advertising its product Coronil as a cure for the novel coronavirus – with the support of the Union health minister.

In a letter to Ramdev, Vardhan asked him to withdraw his statement on allopathy. “The statement disrespects the corona warriors and hurt the sentiments of the country. Your statement on allopathy can break the morale of healthcare workers and weaken our fight against COVID-19,” he said.

Vardhan said that allopathic medicines have saved the lives of crores and described claims that it is responsible for the deaths of lakhs as “extremely unfortunate”.

Previous developments

The Resident Doctors’ Associations of the All India Institute of Medical Sciences (AIIMS) and Safdarjung Hospital too condemned Ramdev’s statement and demanded that “strictest steps” be taken against him.

IMA also said Ramdev saying, “Lakhs of patients have died after taking allopathic medicines.”

Ramdev should be prosecuted under the Epidemic Diseases Act as “untutored” statements are “a threat to the literate society of the country as well as to the poor people falling prey to him”, the IMA said in a statement.

“The Union health minister, who himself is a practising modern medicine allopathic postgraduate and head of this (health) ministry, should either accept the challenge and accusation of this gentleman and dissolve the modern medical facility or boldly face and prosecute the person for his words of arson on the sovereignty of the country and book him under the Epidemic Act to save millions of people from such unscientific utterances,” the IMA said.

The IMA said it has also sent a legal notice to Ramdev, seeking a ‘written apology’ and ‘recall of statements’ by him.

In response to the controversy, the Patanjali Yogpeeth Trust issued a statement, denying the comments and saying, “It is clarified that the truncated version of the video is totally out of context of what is sought to be conveyed by Swami Ji.”

Asserting that Ramdev has “utmost regards” for doctors and support staff working day and night during such challenging times of the pandemic, the statement, signed by Trust General Secretary Acharya Balakrishna said, “Swami Ji has no ill-will against the modern science and good practitioners of modern medicine. What is being attributed against him is false and nugatory.”

IMA also alleged that Ramdev was trying to take advantage of the situation and create a sense of fear and frustration among the people at large, so that “he can sell his illegal and unapproved so-called medicines and make money at the cost of the public at large”. They said that Ramdev deserves to be prosecuted for “disobeying and causing danger” to the lives of many by making them disbelieve the advice of allopathy doctors.

“The IMA demands and resolves if the minister (Harsh Vardhan) is not taking suo moto action, we will be forced to resort to democratic means of struggle to propagate the truth to the common man and knock the doors of the judiciary to get due to justice,” it said, and added that taking people for ransom and winning business by defaming scientific medicine are unpardonable offences.

In a statement, the RDA of AIIMS said it “vehemently condemns” Ramdev’s comments.

“On behalf of the medical fraternity, and all healthcare and frontline workers, we demand strongly that strictest steps be taken against his inappropriate conduct at the earliest to prevent unrest amongst doctors and anxiety amongst the affected patients and their family,” it said.

“Ramdev should be booked under relevant sections of the Epidemic Diseases Act, 1987 and we demand that he offers an unconditional apology to the scientific community failing which we will be forced to call for a public protest condemning the act.”

RDA of Safdarjung Hospital said Ramdev’s statement must be considered as hate speech, and requested appropriate authorities to book him under relevant sections of the Epidemic Diseases Act, 1987.

“We demand unconditional public apology from Ramdev to allopathy and its practitioners,” it said in a statement.

(With PTI inputs)

Note: This article was published at 12:30 pm on May 23, 2021; updated at 7:50 pm on May 23, 2021 to include the Union health minister’s letter; and updated at 8:15 am on May 24, 2021 to include Ramdev’s ‘withdrawal’.

Taking a Page out of India’s Medical History of Courage, Sacrifice and Suffering

Well-equipped hospitals and well-trained doctors and nurses with the courage to make sacrifices like Dr. Yashwantrao and Savitribai Phule alone can save the world and India.

COVID-19 has created a global crisis. We are not sure how the world and India will come out of it. The modern world faced a similar pandemic in late nineteenth century called the bubonic plague, which killed millions in the eastern part of the world – mainly in India and China.

That pandemic also originated in China, in Yunnan province, and spread to many countries through the sea route. Medical facilities at the time were almost all but absent. Particularly in India, there were hardly any trained doctors in modern medicine.

That pandemic spread to all inhabited continents and reached India through the ports at Calcutta and Bombay. Later on, it spread to Pune and other towns and villages. One guess is that more deaths occurred in towns than in spread-out villages, where natural social isolation is already a factor. Several herding communities left urban and populated towns and established settlements in the forest and plain lands.

Though several medical practitioners must have played a role during the time – one young doctor died while treating patients in the Poona region: Mahatma Jyotirao Phule and Savitribai Phule’s adopted son Dr. Yashwantrao.

Also read: Government Measures for Coronavirus Control Leave the Poor High and Dry

The doctor died alongside his adopted mother Savitribai while serving plague patients in a special clinic that they opened in 1896-97. According to historical texts, Dr. Yashwant Rao served patients of all castes and communities as a part of his father and mother’s social reform movement. In those days, Brahmins were avoiding becoming doctors as the British had made it mandatory that medical partitioners  treat patients of all castes, and many Brahmins were unwilling to touch Dalits and Shudras.

The Satyashodak movement launched by the Phules took up a massive campaign against human untouchability and superstitions. Since the couple had no children of their own, they adopted a boy – the son of a brahmin widow, Kashibai. The name of Yashwantrao’s birth father is unknown.

It is said that having while after her husband’s death, conservative Brahmins in the Poona area had wanted to kill his pregnant wife. It was the Satyashodak movement headed by Phule that saved her and took care of the mother and child at their ashram. The son was eventually adopted by the Phules in 1874.

Yashwantrao eventually became a doctor and was married to Radha in 1889, whose father was part of the social reform movement. An inter-caste marriage, it was performed with a simple garland exchange in defiance of being married traditionally by a Brahmin pandit. The priestly class took this marriage to a court also.

Jyotirao Phule died in 1890. After his death, Savitribai and her son continued to undertake social and medical services. One biographer of Savitribai writes:

“Her (Savitribai) adopted son Yashwantrao served the people of his area as a doctor. When the worldwide Third Pandemic of the bubonic plague badly affected the area around Nallaspora, Maharastra in 1897, the courageous Savitribai and Yashwantrao opened a clinic at outskirts of Pune to treat the patients infected by the disease. She brought the patients to the clinic where her son treated them while she took care of them. In course of time, she contracted the disease while serving the patients and succumbed to it on March 10, 1897.”

The tragedy did not end there. Dr. Yashwantrao died as well after contracting the disease. This episode of the bubonic plague ultimately led to more than 12 million deaths in India and China, with about 10 million killed in India alone.

India has evolved a lot since the days of Dr. Yashwantrao and Savitribai Phule’s sacrifice. We now have doctors of all castes and communities. Apart from Dr. Yashwantrao, another doctor to die in the line of duty was Dwarkanath Kotnis during China’s hour of need in the late 1930s. Kotnis was one of the five Indian physicians dispatched to China to provide medical assistance during the second Sino-Japanese war in 1938.

It was on January 10, 1897, that Aldemar Haffkine, a bacteriologist who trained with Louis Pasteur at his institute in Paris, and who was based in Bombay, tested the vaccine on himself and created a vaccine in record time to combat the bubonic plague epidemic in Bombay and Poona regions. That vaccine saved millions in over subsequent years – even though at that time, India superstition and illiteracy coupled with ignorance resulted in restricted use.

The Haffkine Institute is now a premier research and vaccine producing organisation in Bombay.

Also read: Public Health Needs the Public, Modiji, but it Also Needs the Government

Today, coronavirus seems to pose a much bigger threat in a globalised world of air travel in closed air-conditioned aircrafts. Well-equipped hospitals and well-trained doctors and nurses with the courage to make sacrifices like Dr. Yashwantrao and Savitribai Phule alone can save the world and India. And while there is still no vaccine for this novel virus, there will hopefully be one soon.

With some among the ruling party spreading superstitions, we must take a page out of our own medical history of courage, sacrifice and suffering. India still has a long road ahead when it comes to social reform and this crisis is suited to push such reform.

So while there is misinformation about how cow urine and dung work work like a vaccination for coronavirus, people must depend only on tested science, medicines, laboratories, doctors and nurses.

India is a country of 1.3 billion people, among them many who believe in superstitions as part of a long heritage of illiteracy and ignorance. We now have the media, and even mobile networks, informing people about how to look after oneself – from washing hands to not touching faces.

However, casteism and baba-ism will only contribute to loss of more life. As Prime Minister Narendra Modi himself accepted, the Kerala government has been handling the COVID-19 better with a belief in science and medicine. Other state governments must also make adequate preparations.

Kancha Ilaiah Shepherd is a political theorist, social activist and author.

Since September, 3,400 Bottles of Cough Syrup With ‘Poisonous Compound’ Sold

The drug, manufactured by Digital Vision, allegedly led to the death of almost 10 children in Ramnagar area of Udhampur district in the Jammu region.

New Delhi: Close to 3,400 bottles of the ColdBest-PC cough syrup from the batch that is suspected to contain a poisonous compound have been sold since September last year, according to a report in the Indian Express.

“Around 3,400-3,450 (bottles) have been consumed already because the batch was in the market since September,” said Himachal Pradesh drug controller Navneet Marwah and added that the best way to track down consumers was through sales receipts. “But this is an old batch. It’s a 60 ml bottle, so if someone took 5-6 ml in each dose, it would finish in 10-12 doses,” he told the Indian Express.

The drug, which has been manufactured by Digital Vision, allegedly led to the death of over 10 children in Ramnagar area of Udhampur district in the Jammu region between December 2019 and January 2020. After the Centre deployed a team of medical experts to probe the cause of deaths, diethylene glycol was detected in the cough syrup by a PGIMER laboratory.

Production of the cough syrup was soon halted and states, where it had been distributed, were asked to stop its sale.

The owner of the drugs maker Digital Vision, Konic Goyal, has said that the cough syrup manufactured by his company had nothing to do with the deaths of children.

Also read: Nine Children in Jammu Died Because of a ‘Poisonous Compound’ in Cough Syrup

Speaking to the Economic Times, Goyal said that his “company maintains good manufacturing practices standards and hence the syrup could not have led to the deaths of children”.

If the government-run laboratory, where the samples of the syrup have been sent for testing confirms that it was contaminated with the presence of chemical diethylene glycol (DEG), Goyal could face criminal charges.

As per the Drugs and Cosmetics Act:

“Any drug deemed to be adulterated under section 17A or spurious under section 6 [17B] (and which) when used by any person for or in the diagnosis, treatment, mitigation, or prevention of any disease or disorder is likely to cause his death or is likely to cause such harm on his body as would amount to grievous hurt within the meaning of section 320 of the Indian Penal Code (45 of 1860) solely on account of such drug being adulterated or spurious or not of standard quality, as the case may be, shall be punishable with imprisonment for a term which shall not be less than ten years but which may extend to imprisonment for life and shall also be liable to fine which shall not be less than ten lakh rupees or three times value of the drugs confiscated, whichever is more.”.

The Himachal Pradesh government reportedly also plans to file an FIR against the company.

Approximately 5,500 bottles of the cough syrup were sold in the states of Jammu and Kashmir, Himachal Pradesh, Uttarakhand, Haryana, Uttar Pradesh, Tamil Nadu, Meghalaya and Tripura, in September 2019.

The Himachal Pradesh drug controller said that around 1,500 bottles had been seized or recalled. The state regulator has also suspended the company’s manufacturing licence and is asking for six-hourly status reports of the recall. The Central Drugs Standard Control Organisation (CDSCO) is also looking into the issue.

Also read: Why India’s Pharma Industry Needs to Act Now to Win Back the Trust It Lost

While several activists have pointed out lapses in regulatory enforcement, Archana Sahadeva, a lawyer specialising in pharmaceutical litigation, has said that the company would not be absolved even if it turns out that the ingredients sold to it were contaminated since drug regulations mandate that manufacturers test the quality of raw materials.

Dinesh Thakur, a public health activist referred to Digital Vision’s “long and dodgy history of producing NSQ (not of standard quality) drugs” and that authorities had not taken any cognizance of whether manufacturing units were testing the raw materials before using them.

Five batches of Digital Vision Pharma’s drugs that included drugs for diabetes and antibiotics, failed quality tests between 2014 and 2019. Thirteen batches of itn’s drugs were labelled sub-standard in Gujarat and Maharashtra between 2011 and 2019.

Nine Children in Jammu Died Because of a ‘Poisonous Compound’ in Cough Syrup

At least eight states have also been asked to stop the sale and distribution of Coldbest-PC syrup, manufactured by Digital Vision.

New Delhi: After a clinical probe into the deaths of children in Jammu’s Udhampur in January found the presence of a “poisonous compound” in a cough syrup manufactured by Digital Vision, the drug has been halted. At least eight states have also been asked to stop its sale and distribution according to a report in the Indian Express.

“Prima facie, presence of Diethylene Glycol, a poisonous compound, in Coldbest-PC syrup caused the death of children from Udhampur district, PGIMER, Chandigarh, officials have told us,” said Surinder Mohan, the assistant drugs controller, Drug and Food Control Organisation, J&K.

Mohan also said that the samples of the syrup, manufactured by the Himachal Pradesh-based pharmaceutical company, have been sent to the Indian Institute of Integrative Medicine, Jammu, and Regional Drugs Testing Laboratory, Chandigarh, for further tests.

Konic Goyal, the managing director of Digital Vision, told the Indian Express that they “would not like to say anything” on the issue at the moment. The general manager (marketing), Sushil Yadav said, “Production of the medicine has been stopped and we have provided all information to the state drugs control authorities.”

The Jammu and Kashmir Drug Controller Latika Khajuria said that the final report from the Regional Drugs Testing Lab was awaited even though the PGIMER report had located the presence of Diethylene Glycol in the syrup. “Once we receive that report, we will find what actually led to the deaths. The syrup has already been recalled,” she said.

Also read: Why India’s Pharma Industry Needs to Act Now to Win Back the Trust It Lost

In January, almost ten children died of a mysterious disease while six others were taken ill in J&K’s Udhampur district following which the Centre deployed a team of medical experts to probe the cause of deaths.

The Director Health Services (DHS), Jammu, Renu Sharma said that the deaths took place between December-end and January 17 in Udhampur’s Ramnagar block. “The patients were hospitalised with acute renal failure. The common factor found in all the deaths was that they took Coldbest-PC,” she said.

Sharma also said that of the 17 children who had been affected, nine had died.

The presence of an impurity, diethylene glycol, was detected in the cough syrup and found to be present in the solvent propylene glycol (PG), used in the syrup. Its origin has been traced to Chennai-based Manali Petrochemicals. The solvent was sold to two Delhi-based traders, who then sold it to a trader in Ambala, from where it found its way to the Kala Amb-based Digital Vision pharmaceutical unit.

The firm’s manufacturing licence has since been withdrawn.

Close to 5,500 units of the drug are being recalled from eight states and the Himachal Pradesh health safety and regulation authorities have suspended all production at Digital Vision’s unit at Kala Amb in Sirmaur district, where Coldbest-PC Syrup was manufactured.

In a letter to the Himachal Pradesh drugs controller, Jammu’s drugs controller said that after a team of doctors from PGIMER, Chandigarh visited Ramnagar last month to probe the probable cause of the deaths, Diethylene Glycol was found in below pharmaceutical preparation. The letter has also been copied to all state and UT Drug Controllers across India.

Also read: India: the Pharmacy of the World Where ‘Crazy Drug Combinations’ go Unregulated

The team of doctors from PGIMER comprised of experts from the departments of Paediatrics, Community Medicine and Virology. A senior PGIMER doctor, who was a part of the visiting team said that samples of the syrup contained Diethylene Glycol.

“The batch of the syrup believed to be containing the poisonous compound was produced in September 2019. As a precautionary measure, the entire stock is being recalled and production at the factory was stopped on February 17. We are also trying to reach users who bought it,” a Himachal official said.

The Himachal Pradesh drugs controller said that apart from those in Udhampur, no other case related to the cough syrup’s effects had been reported so far.

Haryana DGHS Suraj Bhan Kamboj said the state had banned the cough syrup and the department’s teams were “conducting raids at chemist shops to check availability”.

The Hidden Complications of ‘Evidence-Based Medicine’

Danish physician Peter Gøtzsche was a celebrity in the world of statistical analysis, but some say his views simply went too far.

For eight months in 1975, Peter Gøtzsche recalls driving around Denmark misleading doctors about a new, more expensive type of penicillin. He was 25 years old, with master’s degrees in biology and chemistry. As a pharmaceutical representative for the Sweden-based Astra Group, he was tasked with promoting Globacillin, which was said to be more effective than regular penicillin. At the time, Gøtzsche says he did not know that the claims he was making on behalf of his employer were not backed by high-quality evidence.

Gøtzsche stayed in the pharmaceutical industry for another eight years, writing brochures, strategizing ad campaigns, and, eventually, presiding over clinical trials. It was here that disillusionment set in. Gøtzsche — in his telling, still a principled naïf — would watch with dismay as his superiors twisted or suppressed any unflattering trial results. Increasingly distraught, Gøtzsche began pursuing a medical degree, leaving the industry for good in 1983.

His medical thesis, titled “Bias in Double-Blind Trials,” examined the claims of 244 reports of clinical trials for non-steroidal anti-inflammatory drugs, a group that includes ibuprofen and aspirin. Gøtzsche’s writing strongly critiqued the marketing practices of his former employer, Astra-Syntex, pointing out that no good evidence existed for their claim that the higher the dose, the better the effect.

That thesis was read by an Oxford researcher and physician named Iain Chalmers. It confirmed his impression, Chalmers wrote to Gøtzsche in 1990, that Gøtzsche was “doing extremely important research.” Chalmers, founding director of Oxford’s National Perinatal Epidemiology Unit, had spent much of the preceding decade hand-searching dozens of journals for studies relevant to care during pregnancy and childbirth. His idea was to collect these papers and compile them into reports so that doctors pressed for time would have authoritative, quickly-scannable syntheses of the best available data. In 1993, Chalmers sent an invitational letter to dozens of people, including Gøtzsche, to help found a not-for-profit organization dedicated to gathering and summarizing the strongest available evidence across virtually every field of medicine, with the aim of allowing clinicians to make informed choices about treatment.

They called it the Cochrane Collaboration, after Archie Cochrane, a Scottish epidemiologist and one of the earliest and most prominent advocates for randomized controlled trials, the gold standard of clinical research. Cochrane today has 11,000 members with supporters in 130 countries, and many of the group’s most high-profile findings — that the placebo effect might be a myth; that mammography likely doesn’t decrease breast cancer mortality, and turns healthy women into cancer patients via false or ambiguous findings — emerged from Gøtzsche’s research.

Gøtzsche became the closest thing the world of statistical analysis had to a full-fledged celebrity. His findings were trumpeted, repeatedly, in the New York Times, with his mammography findings even making the front page in 2001. He became the subject of a documentary and was featured in at least one other. “The Daily Show” once had him play a kind of Big Pharma Deep Throat in a segment on the opioid crisis. Viewed by many as a relentless fighter who has accused entire disciplines of nigh-irredeemable corruption, Gøtzsche’s crusades earned him the respect of powerful peers and a loyal following of layperson-skeptics around the world.

So it came as a surprise, at least to outsiders, when Gøtzsche was summarily expelled in fall of last year from the organization he helped found. He was voted off the board, then stripped of his position as director of the Nordic Cochrane Center, Cochrane’s Danish outpost. The stated reason for his termination was, according to a statement from Cochrane’s governing board, “an ongoing, consistent pattern of disruptive and inappropriate behaviours,” along with a breach of the organization’s spokesperson policy, which requires collaborators to clearly identify whether they’re speaking on behalf of themselves or of Cochrane.

The seeming suddenness of his expulsion, and what critics view as its misguided pretext, has exposed rifts that go back decades: debates about the pharmaceutical industry’s influence on medicine and about the research community’s tolerance of dissent. More fundamentally, Gøtzsche’s expulsion has crystalized a longstanding debate about the proper role of data in the practice of medicine.

Gøtzsche’s expulsion sparked debates about the pharmaceutical industry’s influence on medicine. Photo: Reuters

Whatever their differences, Cochrane and Gøtzsche are both vocal supporters of evidence-based medicine, a movement that developed nearly 30 years ago to emphasize the use of well-designed research in medical decision-making. The problem is that neither side, nor really anyone, can agree on exactly what evidence-based medicine ought to mean. Some critics have characterized Gøtzsche as a rigid intellectual who views assessing scientific data as a purely technical task that does not require the input of experts in a given field. Gøtzsche calls such characterizations unfair, arguing that he simply advocates — as everyone at Cochrane should — for the use of rigorous methodology and the elimination of bias in assessing the efficacy of treatments. And while the organization has built its reputation on providing trusted evidence, Gøtzsche now criticizes its methods, accusing Cochrane of bending to industry influence and overlooking important documentation of harms.

“Cochrane’s reliance on published [randomized controlled trials],” Gøtzsche wrote in an email to Undark, “makes Cochrane a servant to industry, which passively promotes what industry wants Cochrane to promote: messages that are very often untrue.”

No one from Cochrane’s leadership agreed to speak with Undark about the Gøtzsche dust-up, or to respond to such charges, but in the organization’s statement accompanying his ouster, they made their position clear: “Cochrane is a collaboration,” the board declared, “an organization founded on shared values and an ability to work effectively, considerately, and collaboratively.”

Gøtzsche, they suggested, didn’t seem to understand that.

In 1992, the Journal of the American Medical Association published a paper titled “Evidence-Based Medicine: A New Approach to Teaching the Practice of Medicine.” With more than 30 co-authors, it advocated “a new paradigm for medical practice,” deemphasizing intuitional and clinical experience in favour of the latest research data. “We believed that the way we were practising medicine was different from how it had been practised before,” the paper’s lead author, Gordon Guyatt recalled, — “fundamentally different.”

The paper had its origins at McMaster University in Ontario, Canada, where David Sackett, an American-Canadian epidemiologist, had been arguing that doctors should be able to make sense of the literature and apply it to their practice. Among other things, this meant studying randomized controlled trials to determine whether an intervention really works.

In a randomized controlled trial, the participants are divided into two or more groups. One group gets the intervention — a drug, for example — and the others get a placebo, a varied dose of the drug, or some other form of treatment. By the 1970s, these trials were a standard component of drug approval. Still, even in the early 1990s, the results had a more modest influence on clinical practice than they do today. According to Guyatt, doctors did not typically keep up with the literature, and drugs were dispensed according to the guidance of local opinion leaders or influence from pharmaceutical representatives. The idea behind evidence-based medicine, then, was for clinicians to consult the literature before making a decision.

Chalmers had been a visiting professor at McMaster in the late 1980s. As the McMaster crew refined and exported their theories, Chalmers began building his own movement, distinct from but parallel to evidence-based medicine, and with significant overlap in ideology and personnel. Its roots lay in the Gaza Strip, where Chalmers had worked as a United Nations doctor in 1969 and 1970. “I believe I would have done a better job, and that fewer of my patients would have suffered, if I’d had access to a good source of reliable evidence for research,” Chalmers said.

Also Read: Gøtzsche Affair Spotlights Challenges of Producing Good Evidence in Medicine

The Cochrane Collaboration was meant to rectify this problem by way of something called a systematic review: all the best randomized controlled trial data on a given treatment, sifted and synthesized into one readable report. “Basically, it was a bunch of troublemaking anarchists who wanted to do something which the establishment was not doing,” Chalmers said. A skilled evangelizer (“In those days, to meet Iain Chalmers was to get hooked to his cause,” said Jos Kleijnen, founding director of the Dutch Cochrane Center), Chalmers had no trouble assembling a global network of like-minded colleagues for his first symposium — Gøtzsche among them.

“The Cochrane Collaboration was an extraordinarily powerful threat against authority,” Sackett told the researcher and author Alan Cassels in his 2015 book on Cochrane. “Individuals who had reputations based upon ‘this is the way this disorder must be treated’ obviously were terribly threatened by what was going to happen with these young upstarts, and kids, and punks, and even laypeople challenging them about what they said must occur in terms of health care.”

The backlash, then, was not surprising. And yet, by the end of the 1990s, the Cochrane Collaboration had attained more or less its present-day esteem, and evidence-based medicine was installed as the dominant paradigm of Western medical practice, a position from which it is has not budged in 20 years. The Collaboration’s efforts were embraced by nurses and younger doctors, who for the first time had a means of challenging the decisions of their elders — what proponents sneeringly called “eminence-based medicine.”

Cochrane, which began as an almost whimsical experiment among a group of like-minded colleagues — an effort, according to Hilda Bastian, one of its founding members, to work out something like the total sum of human knowledge — has morphed, in the course of a quarter-century, into one of the world’s most prestigious medical research bodies, with outposts in dozens of countries and yearly outlays exceeding $1 million apiece from the US, UK, and Australian governments, plus large donations from groups like the Bill and Melinda Gates Foundation, which gave Cochrane $1.15 million in 2016.

Cochrane’s total income last year was roughly $13 million, most of it from royalties on its enormous library of systematic reviews, generated by Cochrane’s global network of research centres and licensed to universities and hospitals around the world. Historically, these research centres have been more or less autonomous, free to pursue their own projects under the Cochrane banner while Cochrane’s main office in London lobbied for and distributed funding.

In recent years, though, Cochrane’s leadership has adopted a more hands-on approach, attempting to centralize the efforts of its far-flung franchises. In November of 2018, 620 disillusioned Cochranites formed Cochrane Members for Change, to protest what one member, Robert Wolff, described in a blog post as a mismatch between these two approaches, “a grassroots science-focused collaboration” on the one hand, and a “top-down more business-oriented” organization on the other. Among this group, Gøtzsche’s termination was interpreted as a troubling symbol of the new business-oriented direction.

Gøtzsche said that Cochrane was “founded on the best of human motives — honesty, generosity, fairness, transparency, openness.” He believes his expulsion will dog the organization for years to come. “It was a fundamental error they made,” he said.

In person, Gøtzsche can be a warm, appealing, gently ironic presence. At 70, he is tall and thin, with a faint dusting of gray hair. Both his eyebrows arch skeptically in the same direction. He delights in bad jokes — “irretrievably bad jokes,” Chalmers said. “Not rude or anything like that; they’re just not funny.” He can be famously good company, and it is not hard to see why so many of the people he has mentored and worked with remain loyal to him. “I just remember [Peter] as one of the most sincere scientists that I have ever met,” said Kleijnen, the Dutch Cochrane Center founding director.

But when it comes to his books and public persona, he also has a famously take-no-prisoners approach. “I dig so deeply in my research,” Gøtzsche said, “that I find the skeletons people have buried down there. And when I put them up on the ground people yell and scream, and call me all sorts of names, because they didn’t think anybody would ever find the skeletons.”

It started with Gøtzsche’s 2012 book on mammography, a recap of the research and controversies attendant to his decade-plus campaign against breast cancer screening. Gøtzsche’s view was, and still is, controversial. His public profile rose a year later with his next book, Deadly Medicines and Organized Crime. It excoriated the pharmaceutical industry, likening its tactics (bribes, kickbacks, serial fraud) to those of the mob.

A woman undergoes a free mammogram for breast cancer detection,March 8, 2012. Credit: Reuters

Gøtzsche’s book on mammography provided a recap of the research and controversies attendant to his decade-plus campaign against breast cancer screening. Photo: Reuters

Gøtzsche’s next crusade had markedly less currency, and planted him, in the eyes of some, on the outer edges of the fringe. Released in 2015, the book was called Deadly Psychiatry and Organized Denial. Its argument, more or less, is that much about the way psychiatry is practised is wrong; that the specialty is built on “myths, lies and highly flawed research”; that the majority of practising psychiatrists are, actively or through ignorance, deceiving and harming their patients, given Gøtzsche’s finding that prescription pills are the third leading cause of death in the US and Europe; and that these same psychiatrists might have noticed some of this were they not helplessly compromised by industry money.

The main reason for the “drug disaster” he writes, is that “leading psychiatrists have allowed the drug industry to corrupt their academic discipline and themselves.” Gøtzsche then goes on to compare the leaders in the field to “primate silverbacks in the jungle” and claims that “psychiatric research is predominantly pseudoscience.”

The psychiatric community had some quibbles with this. Cochrane did, too. When Gøtzsche published a summary of his findings in the Daily Mail, Cochrane’s leadership took the unusual step of publicly distancing themselves through a statement on Cochrane’s website. In addition to stating “unequivocally” that the organization did not share Gøtzsche’s views, it publicly chastised the Danish professor: “He has an obligation . . . to distinguish sufficiently in public between his own research and that of Cochrane — the organization to which he belongs.”

This infuriated Gøtzsche, and the encounter seems to mark the point of no return in his relations with Cochrane management. In the years since, Gøtzsche, who has no special training in psychiatry, has become a fixture on the antipsychiatry circuit, criticizing the discipline in editorials, in presentations, and at various symposia about withdrawing from psychiatric medications. (He has since claimed that almost all Cochrane reviews on psychiatric drugs should not be trusted.) Up until his expulsion, Gøtzsche listed his title in these outreach activities as director of the Nordic Cochrane Center, leading multiple parties to complain to Cochrane itself.

One of these complainants, Fuller Torrey, a researcher at the Stanley Medical Research Institute, a nonprofit that funds work on schizophrenia and bipolar disorder, shared his correspondence with Cochrane’s chief executive. Torrey wrote to call attention to Gøtzsche’s association with an organization called the Hearing Voices Network, which, Torrey claims, “promotes the belief that … auditory hallucinations are merely on end of a normal behaviour spectrum.” Echoing other complaints, he added in a follow-up letter: “It is very difficult to imagine how anyone with these views could possibly be objective regarding a Cochrane study of antipsychotics, thus impugning your credibility which is your most important asset.”

In other words, Torrey seemed to be asking: Is this what Cochrane represents?

Gøtzsche and his defenders argue that Cochrane is not meant to “represent” anything — that Cochrane, as initially conceived, is simply a loose network of independent researchers, who will inevitably hold a range of opinions. But the organization Gøtzsche was forced out of in September of last year was different in crucial respects from the one he’d joined a quarter-century earlier. For one thing, it was no longer called the Cochrane Collaboration. It dropped the latter word in 2015, as part of a broader rebranding effort, and is now known simply as Cochrane.

In 2012, the organization hired Mark Wilson to serve as its CEO. Wilson, who does not have a science background, had spent more than a decade working in operations and development for the International Federation of Red Cross and Red Crescent Societies. In the view of Cochrane’s latter-day detractors, Wilson is the driving force behind the organization’s abandonment of its early, idealistic principles. According to them, he has corrupted the legitimacy of Cochrane’s systematic reviews by kowtowing to pharmaceutical companies and taking a relaxed stance towards conflict-of-interest issues. Former colleagues also describe Wilson as someone who uses business-speak as a weapon, rapidly jargon-ing subordinates into submission. “You can’t get a word in edge-wise,” said Kay Dickersin, another founding Cochrane member and, until it closed last year, the director of the US Cochrane Center.

For his part, Wilson did not respond to multiple interview requests sent by email. Similarly, other members of Cochrane declined to be interviewed. “Having spoken with my colleagues,” Cochrane spokeswoman Jo Anthony wrote in an email, “I understand, at this time, none of them wish to follow up on your polite request and are happy for me to send you this note on their behalf.”

Wilson has been praised for plotting a stable financial future for Cochrane, and for effectively consolidating an unruly, globe-spanning collective of scientists. Even Hilda Bastian — one of Cochrane’s founding members, who parted ways with the organization over the board’s refusal to remove the paywall from the Cochrane Library — noted that Wilson is politically astute. Cochrane “is lucky Mark Wilson hasn’t abandoned them, turned on them,” she added.

“Cochrane started out as a movement,” said Nick Royle, Wilson’s predecessor as CEO. “Over time, it became more business-like, and some of those early adopters perhaps didn’t fit so well into the later framework. That’s just the normal evolution of an organization. That’s just how these things are.”

Gøtzsche has little patience for the new status quo. During a visit this past March, he was highly energized, particularly when discussing what he sees as Wilson’s venality, power-lust, and imaginative bankruptcy. When he isn’t denigrating Wilson, Gøtzsche seems to impute to him an omnipotence somewhat disproportionate to his role as chief executive. In “Death of a Whistleblower and Cochrane’s Moral Collapse,” Gøtzsche’s book-length account of his Cochrane ordeal, Wilson’s regime is compared to those of Voldemort, Big Brother, and Stalin. “He is so powerful that he controls the whole governing board,” Gøtzsche told me. “He controls everything.”

Disagreements over the direction of the organization came to a head last September. Ahead of its 25th annual colloquium, held at Edinburgh’s International Conference Center, governing board members voted to expel Gøtzsche from the organization he had helped turn into a global force. The reason for the expulsion, as related later that month to STAT and Retraction Watch: Gøtzsche had, among other things, used Cochrane letterhead on non-Cochrane-related business, in such a way as to potentially violate the organization’s spokesperson policy.

(An independent legal team hired to review the dispute had not concluded prior to the expulsion that Cochrane’s policy warranted sanction.)

On September 16, the BMJ published a blog post by a researcher who worked with Gøtzsche titled “Cochrane — a sinking ship?” That evening, in Science: “Evidence-based Medicine Group in Turmoil After Expulsion of Co-founder.” And a news article in Nature the next day: “Mass Resignation Guts Board of Prestigious Cochrane Collaboration.” Similar articles were popping up in Italy, Colombia, and Sweden.

Near the end of the conference’s second day, attendees took their seats for the Annual General Meeting in the conference hall’s 1,200-capacity Pentland Suite. About 30 minutes in, the governing board’s co-chair, Martin Burton, took the stage. (The meeting was recorded and posted on YouTube.) Gøtzsche recounts in “Death of a Whistleblower” that before the meeting, he and David Hammerstein — a fellow board member who’d resigned upon Gøtzsche’s expulsion — had gathered signatures for a vote of no confidence in the present board, and the establishment of a new one right there in the conference hall. At Gøtzsche’s signal, two of his colleagues were to stand and set the process in motion.

Gøtzsche lifted himself from his seat and signalled to his colleagues across the room. But the colleagues stayed seated. (Neither would comment for this article, but in his book on the expulsion, Gøtzsche suggests that at least one, Karsten Juhl Jørgensen, was worried about Wilson taking retributive action.)

No coup materialized. About a week later, Gøtzsche was formally booted from the board. About a month after that, he was summarily fired from his job as the director of the Nordic Cochrane Center.

The Cochrane/Gøtzsche split has by now been made to bear the weight of a number of disparate narratives by the journals and the medical press. One popular narrative posits Gøtzsche as a truth-seeking maverick — the spirit of evidence-based medicine incarnate — going up against the creeping commercialism and bias-tolerance of mainstream science. Peter “is willing to take positions that are sometimes very unpopular and probably create a lot of anxiety and even enmity in some circles,” said John Ioannidis, a Stanford professor and prominent supporter of evidence-based medicine. “We need people who are willing to take unpopular positions and provide the data.”

Another narrative describes Gøtzsche as a practitioner of an older, perhaps outmoded model of evidence-based medicine in which reviewing study data is viewed as a narrow task — as, essentially, math — which has since been superseded by the more open, pluralistic version supposedly taken up by Cochrane since Wilson’s hiring.

Both views were recently unpacked in a 2019 paper published in the Journal of Evaluation in Clinical Practice. The paper’s corresponding author, University of Oxford professor Trish Greenhalgh, has in recent years emerged as one of the most prominent internal critics of the direction the evidence-based medicine movement has taken since its inception. In the 2019 paper, she takes particular issue with how the movement prioritizes clinical trial data over and above a physician’s intuition or knowledge.

(Greenhalgh said she could not comment for this article, citing the possibility of a legal challenge to her piece from Gøtzsche. Gøtzsche, in a private, 11-page rebuttal he sent to Greenhalgh, which he shared with Undark, claims that the article is “libellous” and “riddled with biases, errors and inexcusable oversights.”)

Evidence-based medicine’s detractors further point out that its very name makes it difficult to criticize. “How do you argue against evidence-based medicine?” asked Mark Tonelli, a professor of medicine at the University of Washington. One way would be to destabilize the very concept of “evidence.”

Randomized controlled trials, which are typically conducted by scientists who don’t practice medicine, and often funded by people who want to sell drugs, are not designed with the patient in mind. For one thing, as Tonelli pointed out, these trials tend to weed out patients with more than one illness, meaning these drugs are being tested on people who bear little resemblance to huge swaths of the patient population. (“What elderly diabetic patient doesn’t have comorbidities?” asked Tonelli.) And as Greenhalgh pointed out in a 2014 paper titled “Evidence-Based Medicine: A Movement in Crisis?” — which set off a fervent round of soul searching in the evidence-based medicine community — the results of randomized controlled trials may be “statistically but not clinically significant.”

More importantly, according to these same critics, in elevating randomized controlled trials, the evidence-based medicine movement has consciously demoted all other forms of knowledge: observational studies, clinical experience, and the unique, un-averageable needs of the patient on the other side of the doctor’s desk. Greenhalgh suggests, in her Journal of Evaluation in Clinical Practice paper, that this has lately begun to change, citing an “epistemic crisis” in the movement. Gøtzsche, she argues, is trying to resist the “epistemic forces” that are redefining his world.

The implication is that in sacrificing Gøtzsche, Cochrane is taking a step towards a reformed, less aggressively doctrinal evidence-based medicine. The problem, from what Gøtzsche has argued, is that he agrees with much of what Tonelli and Greenhalgh have to say. Rather than relying solely on randomized controlled trials, he says, “observational studies and case reports can be very important for finding harms.”

In any case, exactly how dismissing Gøtzsche would lead to any real change in Cochrane is unclear, as is any specific way in which this “epistemic crisis” has led to tangible changes for the better. According to Tonelli, these concerns have not trickled down to clinical practice. For people like Greenhalgh in particular, there’s a feeling that this “can be solved,” he said. “For me, it’s more of a true epistemic limitation and the only way to get past it is to acknowledge the severe limitations of clinical research for practice and then re-broaden our approach to how we view medical knowledge.” Despite being primarily targeted at patients, the conclusions of “Deadly Psychiatry” might provide one example of an evidence-based medicine troublingly abstracted from real people’s needs.

David Healy, a psychiatrist, prominent psychiatry critic, and sympathetic ally of Gøtzsche’s, pointed out that “if you’re not constrained by the need to actually treat people” and don’t see that medications can be helpful, “then it’s easy to drift into thinking it would be best if we didn’t have them. And I think Peter has toppled a little bit too much over that way.”

This past March, Gøtzsche launched an organization called the Institute for Scientific Freedom, which aims to “preserve honesty and integrity in science.” It was part of Gøtzsche’s campaign to avenge himself for the perceived wrongs visited upon him by Cochrane, and to further the work he once did at the Nordic Cochrane Center. (The article he wrote to announce the institute, published on the psychiatry-skeptic website Mad in America, contained 12 paragraphs on his expulsion from Cochrane and on Cochrane’s perceived moral rot, and roughly one sentence on what the institute would actually consist of.)

Gøtzsche’s home, 20 to 30 minutes by car from the centre of Copenhagen, hummed with activity on the afternoon before the institute’s opening symposium, which was to be held the following day. Among those milling about the kitchen were Peter Wilmshurst, the British cardiologist who in 1986 had blown the whistle on Sterling-Winthrop, a drug company which had tried to suppress his negative findings about the cardiac drug amrinone. (He was able to blow the whistle a second time, two decades later, when a medical device company that had recruited him for help tried passing off misleading data.)

Also in attendance was the US psychiatrist Peter Breggin, who at 83 years old, is still capable of generating controversy — as when, last year, he served as an expert witness for Michelle Carter, the woman who, as a teenager, pressured her boyfriend into killing himself. (Breggin has made his name in part as an expert witness for people who commit crimes while on prescription drugs, which Carter was at the time.)

Pamela Popper, another of the next day’s lecturers and a prominent advocate for healthy eating as a substitute for medication — and a business partner of Breggin’s — was also visiting. A naturopath, Popper runs a popular YouTube channel, and it had driven some of sign-ups for the next day’s conference. She wasn’t surprised, she said, by what happened to Gøtzsche. “We’ve all been come after,” she said. “It’s a badge of honour really, to be pursued by them. It must mean you’re doing something right.”

With Gøtzsche, of course, the pursuit is reciprocal. He is infamous for coming after people, even his own colleagues. Two months before Edinburgh, Gøtzsche co-authored a critique of Cochrane’s recent HPV vaccine review, which had concluded that “there is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and women.” Gøtzsche’s paper accused Cochrane’s researchers of excluding nearly half the relevant trials and incompletely assessing certain adverse events and safety signals.

HPV vaccines in Sao Paulo, Brazil, March 2014. Credit: pahowho/Flickr, CC BY-ND 2.0

HPV vaccines in Sao Paulo, Brazil, March 2014. Credit: pahowho/Flickr, CC BY-ND 2.0

From all the available evidence, this paper was not the cause of Gøtzsche’s expulsion. His two co-authors, also members of Cochrane, were not removed from the organization. The news coverage, though, tended to link the two events, and Gøtzsche was subsequently taken up as a hero by anti-vaccination groups, who assumed he shared their worldview. The Danish researcher appeared to outside observers not to be at pains to disabuse his new followers of this notion. If anything, he appeared to be courting it.

A few weeks before the symposium, Gøtzsche’s face had cropped up in the promotional materials for a workshop run by Physicians for Informed Consent, a prominent anti-vaccination group, to be held just a few days after the opening of his institute. Gøtzsche was to deliver its keynote, alongside such anti-vaccine luminaries as Toni Bark and Robert F. Kennedy Jr. When the news was picked up on Twitter, Gøtzsche quickly pulled out. When asked about it, he claimed he hadn’t realized who the other speakers would be.

The Institute for Scientific Freedom’s symposium was held at Bethesda, a historic church in central Copenhagen. The one-day event was to be made up mostly of short talks (sample titles: “Medical journals are an extension of the marketing arm of pharmaceutical companies”; “The many forms of scientific censorship in psychiatry”) with two audience Q&As, one before the lunch break and one at the end. There were about 80 or 90 people in attendance, some who appeared to be in their 20s, but most who looked to be at or beyond middle-age. Gøtzsche, appropriately, looked nearly priestlike, standing on the stage in all-black.

The fact that Gøtzsche had inadvertently organized a kind of impromptu anti-vaccination convention became clear during the first Q&A, after the fourth or fifth successive question about vaccines. One questioner asked Peter Aaby — who conducts vaccine research in Africa — why, given the apparent abundance of studies showing that measles is actually good for you, we don’t try and study what happens when you give certain African children large doses of Vitamin C instead of “injecting them full of toxins” (i.e., giving them the measles vaccine).

“Could I perhaps ask also for questions about … not vaccines?” Gøtzsche asked eventually.

The next questioner promptly took the mic and said they had a question about vaccines.

“Please, please, please talk about something else now!” said Gøtzsche.

“I just want to say that the BCG part of tuberculosis, which is in the BCG vaccine, was never on the schedule in the US, and tuberculosis was the number two killer in — ”

“But please, excuse me, this is still — ”

The woman talked over him, so Gøtzsche raised his voice to match: “I ask you very kindly to not ask a question about vaccines at this point in time.”

Iain Chalmers had flown in from London to attend the event. He’d had to duck out early, but said later by phone that he had been troubled by much of what he’d managed to see.

The older psychiatrist, he said, referencing Peter Breggin, “basically, he seemed to feel that undying love was a good treatment for psychosis.” And referencing Pam Popper’s talk: She seemed to think “you could stay healthy all your life if you eat the right foods.” Not to mention the audience, and their worryingly sustained applause at certain lines from the stage, notably those seeming to be against vaccination.

It had become clear to Chalmers, at least, that in taking on the establishment, Gøtzsche had attracted the wrong crowd. He didn’t mention any of this at the conference. But before leaving for the airport, Chalmers relayed one bit of tough-love advice: namely, that Gøtzsche should reconsider making himself the public face of his new organization. Nothing against him — it’s just, he isn’t much of a showman. Sort of an anti-showman, really.

There had been plans to publish a transcript of the Q&A, but these were quickly scuttled — “too embarrassing,” Gøtzsche admitted later. The whole thing seemed to alarm him. “We were quite disturbed by these people,” he said.

Gøtzsche had some trouble getting his recent book, Survival in an Overmedicated World, published in English. He said he never needed an agent before, but had to hire one this time. After a round of rejections, Gøtzsche says, the agent informed him that American publishers thought it somewhat irresponsible to publish a manual about how to bypass doctors and seek out the best medical information via the internet. “You should not trust your doctor. You should look up the evidence yourself,” he told me, explaining the book’s thesis.

This project might represent, depending on your perspective, either the vilest perversion or the perfect apotheosis of the evidence-based medicine ethos. If we reduce the practising doctor to an algorithm, mechanically relaying the relevant treatment as prescribed by the latest data, then dispensing with that doctor — with her biases, her blind spots, her susceptibility to the latest marketing or lobbying efforts — seems a sensible next step.

The book has appeared in several languages, with the English version published at the end of April. Its opening paragraph is instructive:

“‘You do not ask a barber if you need a haircut.’ Most people have heard this expression or something similar. Yet we willingly allow our doctors to subject us to various diagnostic investigations and treatments which may be financially beneficial for themselves. Health care is riddled with financial conflicts of interest, and even when your doctor does not directly benefit, there are many other reasons you should be on the alert.”

Having started his career critiquing the drug companies, Gøtzsche’s circle of scorn has since widened to take in mammographers, psychiatrists, scores of his own colleagues, and, now, seemingly every single doctor in the world. According to him, he has another book — Vaccines: Truth, Lies, and Controversy, coming out in February.

As for whether he’s through with Cochrane, Gøtzsche said: “It’s not over yet.”

Daniel Kolitz is a writer living in Brooklyn.

This article was originally published on Undark. Read the original article.

Neuroscience Should Take Sex Differences in the Brain More Seriously

Diseases like Alzheimer’s and schizophrenia manifest differently in men and women, and that’s important to know.

As a neuroscientist who identifies as a woman, I love that there is discussion of dismantling the patriarchy and supporting diversity for those working in STEM. But, as a neuroscientist who studied the neurobiology of postpartum depression and how hormones affect the brain, there’s another layer to the issue of sexism in the field that we have to talk about: diversifying our research subject pools.

Neuroscience has historically had a problem of predominantly using male test subjects, from studies of how the brain works to what happens in brain illnesses. The field then assumes that whatever has been true for them will be true for everyone else. This assumption is dangerous.

Why did it take women struggling before researchers realised that sex differences exist in the first place?

Take the drug zolpidem (trade name: Ambien) to treat insomnia. When the medication was first released in 1992, doctors provided men and women with prescriptions of equal doses of zolpidem, and hoped that this would alleviate their sleep troubles. But, no such luck… for women. Women began reporting adverse effects ranging from hallucinations to sensory distortions because the drug was not clearing out as quickly from their bodies. In 2010, women accounted for 68% of ER visits related to zolpidem. Researchers are still not entirely sure why women are more sensitive to it; hypotheses range from differences in how men and women’s liver enzymes work, body weight differences, and even testosterone levels. Nonetheless, the FDA now recommends that women should be prescribed smaller doses than men.

Similar issues have come up with different responses to antidepressants, identifying symptoms of autism, and understanding how Alzheimer’s disease happens.

Some medications, like Ambien, affect men and women differently. Credit: Freestocks.org on Unsplash

But, the bigger question is why did it take women struggling before researchers realised that sex differences exist in the first place?

Before we answer that question, we have to talk about what sex differences are. Sex refers to the biological condition of one’s sex chromosomes, with XY generally classified as male, XX as female, and expressions like XO or XXY as intersex (XX or XY individuals can be intersex as well). Gender refers to how one identifies and is influenced by societal and cultural factors. Sex differences in the brain refer to when features of the brain – like chemical levels, hormone receptors, or immune activity – are present in everyone, but biological sex influences how much they are present. For example, sex chromosomes affect production of hormones like testosterone and estrogens. Everyone has different levels of both hormones which can affect all organs of the body, including the brain. It’s not only hormone levels, either. There are sex differences in how the brain processes the stress response, activity of chemicals like dopamine and serotonin, and even how the immune system interacts with the brain.

Biological sex affects many aspects of how our brains work. Credit: Ken Treloar on Unsplash

And yet, neuroscience has long evaded including a diverse group of participants, members of all sexes, in experiments.

A 2017 study on sex bias in neuroscience research analysed leading journals in the field and found that for rat and mice models, which account for approximately 50% of neuroscience research, the majority failed to use biological sex as a statistical variable or acknowledge the sex of the animal. Omitting sex as a variable in data analysis means that valuable information about whether a discovery was relevant or not to a particular sex gets lost. Failing to report the biological sex of the subjects creates chaos in trying to replicate and build upon findings. And casually discarding data should bother everyone.

There is understandable concern about how academic institutions and their deeply rooted misogyny will use this information

Considering biological sex as a factor in research has been revelatory for understanding the brain. Neurological and psychiatric conditions such as autism, Alzheimer’s disease, schizophrenia, depression, and Parkinson’s disease are characterised by sex differences in the prevalence of the disease, how if manifests, and even how effective treatments are. In my own research, I’ve studied depression, an illness that affects twice as many females as males, with particular vulnerability around times of hormone shifts like puberty and pregnancy. Using a rat model of postpartum depression, I found that after the huge hormone changes of pregnancy and postpartum, traditional antidepressants weren’t as effective in the brain, a concern for the 15% of mothers struggling with postpartum depression.

But, there is understandable concern about how academic institutions and their deeply rooted misogyny will use this information. Will differences be exploited as biological proof one group is better than the other? More capable than the other? Will differences be used to categorise what’s “normal” and consequently discriminate other groups as “abnormal”?

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These fears have sparked a counter-argument, calling for researchers to abandon studying sex differences in the brain. Researchers like Gina Rippon, a professor in cognitive neuroscience at Aston University in the UK, claim that researching sex differences is a form of “neurosexism” and that the evidence of biological sex affecting the brain is a “myth.” Not only is this problematic because it undermines the growing body of evidence that researchers have been conducting to rectify the historical sex bias in neuroscience research, it creates confusion for how today’s neuroscientists fix the problems of the past. And it does so by conflating equality with conformity, aka to treat everyone as “equal” means they must all be “identical to men.”

I understand why their fears exist. Oppressors have long distorted neuroscience to fit their claims of superiority and use it as means to justify oppression. And shamefully, it’s not even that old of a problem. The infamous 2017 Google memo claimed that sex differences in the brain meant women were biologically incapable of being equal to men in performing in the technology sector. Only last year, a professor from the European Organization for Nuclear Research, or CERN, argued that women’s brains were fundamentally inferior in studying physics as an explanation for why there are fewer women physicists relative to men. They brushed off gender inequality in their fields as the nature of the oppressed rather than systematic barriers nurtured by the oppressors.

Turning a blind eye to how sex and gender affect the brain as a solution to sexist interpretations of data is akin to pretending to not see people of color as a solution to racism.

This fear is also relevant to the LGBTQIA+ community. Sex and gender are more complex than “male” and “female” (check out this infographic from Scientific American). Biological sex is often assigned based on what the gonads look like at birth, not necessarily based on genetics. So, intersex conditions may not become apparent until later in life. Neuroscience research has been informative for sensory function during gender confirmation surgeries. But, biomedical research has historically been conducted to further marginalise those who don’t identify with their sex assigned at birth or conform to heteronormative conditions. Fear that neuroscience research will be used to further isolate them, or worse, treat their identities as deviations from a false dichotomy of “male” or “female” is anti-scientific.

The questions that plague neuroscience research – How can we cure neurological and psychiatric disease? Why aren’t the current drugs working? – are questions that demand more data. Turning a blind eye to how sex and gender affect the brain as a solution to sexist interpretations of data is akin to pretending to not see people of color as a solution to racism. Does it conveniently allow for those in power to sweep marginalised groups under the rug and call it equality? Yep. Does it actually fix the problem of inequitable research? Nope.

Studying the brain is a messy, but necessary, endeavor. Credit: Jesse Orico on Unsplash

There also is an argument that researchers should abandon studying sex differences because gender is more influential than biological sex in the human brain, stemming from confusion about “nature” vs. “nurture” in the brain. Nature refers to things that are usually present before we’re born, like sex chromosomes, whereas nurture refers to things we encounter as we grow up, like sociocultural influences around gender. The brain is tremendously plastic, with connections rewiring moment to moment. Both biology and environment influence how plasticity happens in the brain, not simply one or the other.

Here’s the truth: studying the brain is messy. It’s messy because literally everything – from DNA to culture to gender to your childhood – affects how it works. Parsing out these differences seems messy but actually provides a more nuanced and accurate understanding of the brain. As feminists and neuroscientists, we must work towards the ideal of equitable research so that everyone benefits from neuroscience. Studying sex differences isn’t the magical last step to solving the mysteries of the brain, but it is a part of the puzzle that is valuable.

We’re all different. And those differences aren’t going away by blindfolding the data to those differences.

This story originally appeared on Massive Science, an editorial partner site that publishes science stories written by scientists. Subscribe to their newsletter for even more science delivered straight to you.

Government Notifies New Rules for Drugs and Clinical Trials

“The aim is to promote clinical research in India, have predictable, transparent and effective regulations for such trials and also make faster accessibility of new drugs to the Indian population.”

New Delhi: Aimed at promoting clinical research in the country, the health ministry on Monday notified the New Drugs and Clinical Trials Rules, 2019, reducing the time for approving applications to 30 days for drugs manufactured in India and 90 days for those developed outside the country.

The new rules will ensure patient safety, as they will be enlisted for trials with informed consent. The ethics committee will monitor the trials and decide on the amount of compensation in cases of adverse events, Drugs Controller General of India (DCGI) S. Eswara Reddy said.

“In case of injury to a clinical trial subject, medical management will be provided as long as required as per the opinion of the investigator or till such time it is established that the injury is not related to the clinical trial.

“Also, compensation in cases of death and permanent disability or other injuries to a trial subject will be decided by the Drug Controller General,” Reddy said.

Also read: Explainer: Rahul Gandhi’s Three Promises and One Criticism on Healthcare

These rules will apply to clinical trial, bio-availability or bio-equivalence study, new drugs and regulation of ethics committee relating to clinical trial and biomedical health research.

“The aim is to promote clinical research in India, have predictable, transparent and effective regulations for such trials and also make faster accessibility of new drugs to the Indian population,” he said.

These rules provide for the disposal of clinical trial applications by way of approval or rejection or seeking further information within 90 days for drugs developed outside India.

However, in case of an application for conducting a clinical trial of a new drug or investigational new drug as part of discovery, research and manufacture in India, the application is to be disposed of within 30 days.

In case of no communication from DCGI, the application will be deemed to have been approved, the rules stated.

The requirement of a local clinical trial may be waived for approval of a new drug if it is approved and marketed in any of the countries to be specified by the DCG with the approval of government from time to time and certain other conditions.

A local clinical trial may also be waived if the application is for import of a new drug for which the DCGI had already granted permission to conduct a global clinical trial which is ongoing in India and in the meantime the new drug has been approved for marketing in a country specified by the DCGI and certain other conditions.

The Dark Side of India’s Indigenous Sex-Selection Drug Preparations

Traditional medicines are not subjected to regulation of chemically defined compounds. Indigenous preparations pose important ethical questions, especially when it comes to sex-selection drugs as it can lead to congenital malformations.

While pharmaceutical formulations are regulated for their chemically defined compounds, traditional medicines circulate on the foundation of faith and desire. The use of these uninvestigated indigenous preparations (IP) forms an integral part of an alternative health care system that targets a vulnerable chunk of the population. These preparations are often put to unethical use and serve a big blow to our long fight against social evils.

A striking example is the consumption of IPs in the form of sex-selection drugs by expectant mothers in the hope of a male child. Though the Pre-Conception and Pre-Natal Diagnostic Techniques Act has been in place for almost 24 years, the country still grapples with prenatal sex selection and female foeticide, posing a risk to the health of newborns and mothers.

Sutapa Bandopdhyay Neogi, Indian Institute of Public Health – Delhi, Public Health Foundation of India, and her team have been studying the causes of congenital malformation in the state of Haryana for several years. The researchers had earlier found that consumption of sex-selection drugs by women during pregnancy was associated with 25% of children being born with structural abnormalities.

“We were quite convinced of the harmful effects of the IP,” says Neogi, “While we initiated animal model studies, we also thought it would be fruitful to start investigating the chemical components contributing to the effects”. The group found alarming quantities of lead and mercury in three traditional drugs containing Shivalingi (Bryonia laciniosa), Majuphal (Qtuercus infectoria) or Nagkesar (Mesua ferrea) as their major components. Quite infamously, Haryana suffers from a severely skewed female to male ratio of 832:1000 (compared to the national average of 898:1000).

Exposure to heavy metals is a cause of major concern for pregnant women. In the aforementioned indigenous preparations, lead quantity was roughly tenfold higher while mercury was four hundred-fold higher than the recommended FDA levels. Such high maternal loads of heavy metals can cross the placental barrier and damage the developing fetus, especially in the first trimester, when these drugs are usually consumed.

The presence of heavy metals is not the only concerning factor. An earlier study by the same authors reported the presence of phytoestrogens in these formulations, which are chemicals that mimic natural hormones and can cause hormonal imbalances in pregnant women, potentially even leading to sterility. A few samples even contained testosterone, a hormone strongly contraindicated during pregnancy.

Neogi’s team previously explored the demographics of consumption of such sex-selection drugs in a population-based study. Approximately 40% of the mothers who consumed these drugs had received primary education while most fathers were manual labourers. The paper reported that the risk of having a child with congenital malformations was increased threefold among mothers who had a history of IP intake. Moreover, the statistics from the study suggest that the risk of malfunction is stronger for a family with a prior girl child.

The claims of these alternative drugs are brazened and can be misleading. Even a quick internet search leads to websites like this which propound the use of Shivalingi seeds as “putr jeevak” (male birther). Shivalingi is also touted as a sexual prowess enhancer. While published experiments using male rats indicate that Shivalingi can increase testosterone levels, this may have unintended consequences. “With the overload of steroidal hormones, the drugs can potentially influence the reproductive fertility in adults. However, they are detrimental to the development of reproductive organs of the fetus,” says Neogi. “More research is needed to scrutinise and verify the biological effect of individual components. To investigate at a molecular level, we need funding and are actively looking for collaborations,” she adds.

It is imperative to state here that sex of the developing fetus cannot be altered by any drug. The chromosomal combination that determines the sex of the fetus is sealed at the time of fertilisation. An informational video about this process was created as part of a project supported by the Department of Science and Technology.

This article originally appeared on IndiaBioscience, a non-profit initiative engaged in science outreach and communication. You can read the original article here.