Monthly Archives: April 2022

After dodging COVID-19 several times during the pandemic, flight attendant Angeliki Kaoukaki wondered if she was a medical anomaly. But shes possibly among a small group of people who might have genetic resistance to the virus. Scientists are now racing to understand how such resistance to COVID-19 could workand whether the trait can be harnessed to develop new drugs against the disease.

Kaoukaki had already worked alongside other cabin crew members who tested positive without getting sick herself. Then in July 2021 Kaoukakis partner contracted a severe case of COVID-19 with high fever and unbearable pain that lasted nearly 10 days. Kaoukaki showed no symptoms, despite the fact that the pair isolated together for two weeks in their studio apartment in Athens, Greece.

She continued to test negative on multiple PCR and rapid antigen tests, and a test she took 23 days after her partners confirmed infection revealed no antibodies in her blood.

Every day I heard [from doctors] that maybe you have COVID, she says, but again and again, I tested negative.

Despite both being vaccinated,her partner got COVID-19 again during the Omicron wave in January. Kaoukaki isolated with him for five days and again showed no symptoms and continued to test negative for the virus. Thats when she began hunting for an explanation.

Anonline articleled her toEvangelos Andreakos,an immunologist at the Biomedical Research Foundation of the Academy of Athens. He is part of an international consortium called the COVID Human Genetic Effort that has been looking for genetic variations that might reveal why some people never get COVID-19.

Although Andreakos and his colleagues didnt expect to find many such individuals for their study, they were overwhelmed with emails from at least 5,000 volunteers worldwide with stories similar to Kaoukakis. Using saliva samples from the 20 percent of people who met their study criteria, Andreakos and his team will be scanning the protein-coding regions of genes in their DNA to spot any mutations that are absent in the genetic sequences from patients who had severe or moderate cases of COVID-19. The hope is that some of these people harbor the secret to COVID-19 resistance.

We expect it to be a rare population, Andreakos says. But there are precedents.

For a long time, the outcome of any infection was assumed to depend on the genetic traits of the pathogen.

There used to be a tendency to more think about the pathogen in terms of severityit's a severe pathogen or a mild pathogen, says molecular virologist Johan Nordgren at Swedens Linkping University. Relatively less attention was paid to a host and whether their genes affect their ability to fight off an infection, he says.

In the last two decades or so, though, scientists have been conducting so-called genome-wide association studies to identify certain genes or regions of DNA that may be linked to specific diseases. They do this by comparing the genetic sequences of infected individuals with those who are healthy and seeking correlations between mutations and resistance.

In 1996 this method enabled molecular biologist Stephen OBrien and his colleagues to discover a rare genetic mutation that protects against the human immunodeficiency virus that causes AIDS.

Most people have a protein receptor present primarily on the surface of certain immune cells called the chemokine receptor 5, or CCR5. This receptor allows HIV to bind with and enter the cell. But O'Briens team discovered that some people have a mutation that produces a defective receptor.

To be resistant, an individual needs two copies of this so-called delta-32 mutationone from each parent. A single copy can still allow the virus to infect cells, although it slows down the patients trajectory to developing AIDS.

Delta 32 was a hell of a good example that convinced people that genetics was important and that it was possible to have a genetic resistance, OBrien says.

Scientists have also tracked down a mutation in a different gene that confers resistance to certain norovirus strains that are a major cause of acute gastroenteritis worldwide. This mutation prevents noroviruses from entering the cells lining the human digestive tract.

In other words, you either make the port the virus uses to get into the cell, or you do not, says Lisa Lindesmith, a norovirus researcher at the University of North Carolina at Chapel Hill. If you don't, it doesn't matter how much virus we can give you, you do not get infected.

While genetic resistance to viral infections isnt widespread, the fact that it happens at all has ignited interest in similar mutations in COVID-exposed individuals.

The COVID Human Genetic Effort started recruiting volunteers last year, with a focus on healthcare workers who were exposed to the virus but didnt get infected, and healthy adults living in a household with a spouse or partner who got sick and experienced moderate or severe COVID-19 symptoms, like Kaoukaki.

The scientists hypothesized that if these individuals were repeatedly exposed and still escaped infection, they were more likely to carry a mutation that confers resistance to the virus.

One promising target is the gene that codes for the human ACE2 receptor and those that regulate its expression on cell surfaces. The SARS-CoV-2 virus that causes COVID-19 must bind to ACE2 to enter cells and infect them. A mutation that alters its structure and expression might block the virus from binding and prevent infection.

So far, ACE2 seems to be our best bet, says Jean-Laurent Casanova, a geneticist at Rockefeller University who is part of the COVID Human Genetic Effort. Genetic variations that allow ACE2 to function normally but disrupt its interactionwith the virus"these would be good candidate genes, he says.

Its possible, though, that there are other biological factors aside from the ACE2 receptor that could explain why some people didnt develop a SARS-CoV-2 infection.

Some people may possess a robust immune system that produces antiviral proteins called type I interferons, which limit the virus from replicating in human cells. Theyre the bodys first line of defense and appear even before antibodies form against the virus.

Another hypothesis is that immune cells called memory T cells that may have formed during previously encountered coronaviruses, like those that cause the common cold, help limit SARS-CoV-2 infection in certain patients.

In 2020, prior to the vaccine rollout, one study found greater presence of memory T cells in healthcare workers who were exposed to the virus but who didnt develop COVID-19.

The memory T-cells may have cleared the virus very quickly for a few people. But its no guarantee these people will be protected from future infections. In fact, we know some have gone on to get infected with more infectious variants and/or perhaps with a higher dose of the virus, says Mala Maini, a viral immunologist at the University College London and one of the study authors.

If their study does turn up clues to genetic resistance, Casanova hopes that information could be used to develop therapeutics against COVID-19, similar to the CCR5 inhibitors designed to treat HIV infections. But decisions to develop these therapies, Casanova says, will depend on the nature of the mutated genes discovered.

See more here:
Are some people resistant to COVID-19? Geneticists are on the hunt. - National Geographic

Professor Knoppers, born 71 years ago in Hilversum (The Netherlands) and raised in Canada, is an international reference point for the moral dilemmas involved in genetic engineering.Consuelo Bautista

Just over three years ago, Chinese scientist He Jiankui surprised the world by announcing that the first three genetically modified babies had been born; their genome supposedly edited to make them immune to the AIDS virus. For Professor Bartha Knoppers, a world authority on the ethical aspects of genetics, genomics and biotechnology, the verdict was clear. Jiankuis intervention was unnecessary and sloppy, deserving of the prison sentence and the almost unanimous contempt of his colleagues that it received. On other occasions, the ethical line is much harder to draw.

She participated in writing the Universal Declaration on the Human Genome and Human Rights, which was adopted by the United Nations in 1998 and prohibits human cloning. More recently, she has been a member of the international commission created after the He Jiankui scandal. The expert group warned that gene editing techniques are still not safe, but left the door open for modifying the genes of children to avoid lethal diseases. Knoppers, director of the Center for Genomics and Policy at McGill University in Montreal (Canada), passed through Barcelona on March 21 to speak at a conference at the Center for Genomic Regulation.

Question: American chemist Jennifer Doudna (the mother of the CRISPR technique, which makes cheaper and relatively accurate gene editing possible) says she has had nightmares in which Adolf Hitler, covered with a pig mask, is asking her for more information about her invention. What nightmares do you have about genome editing?

Answer: I dont have them. Im optimistic. Perhaps I am too romantic. But, on the whole, the scientists I have worked with all my life are wonderful and very responsible people. Im sure there are scientists who have evil intentions, but I have not met them. Sometimes we assume the worst of futures and try to make regulations from that assumption, but this isnt the way to manage these new technologies - I dont take the approach that something monstrous is going to happen.

Q. We have the example of the Chinese scientist He Jiankui.

A. There are irresponsible scientists and he is an example, but an irresponsible scientist or two cant taint all those who are trying to advance medicine.

Q. Are you in favor of editing the human genome in such a way that the changes are inherited by following generations?

A. I was part of the international commission that prepared a report in 2020. We said that at the moment there is no safe and effective way to edit the germline (modifications that take place in the eggs, sperm or embryos themselves when they are only a single cell and that are then inherited by subsequent cells). So, at this point, I dont support any intervention that hasnt been shown to be safe and effective before it is applied to humans.

Q. Using the CRISPR technique, He Jiankui modified the genome in three babies. Nobody thinks that these children will be the last. How do you think the fourth baby will be CRISPR-ized - when, in what country, and for what reason?

A. I dont think about it. We have so much work to do in supporting responsible science that I dont want to spend my life predicting what can go wrong and creating collective imaginaries, like the movies. I dont want to create science fiction about CRISPR because the more you talk about it, the more it seems real. I prefer to be creating regulatory frameworks and laws to ensure that science never enters areas that are harmful to human beings.

Q. The question was positive: if you imagine that the fourth CRISPR-ized babys genome is modified to avoid a disease, for example.

A. It could be. We discuss this possibility in our report, but the situations in which a couple would need CRISPR to modify their childrens embryos are extremely rare, so its actual usefulness is extremely low. So why work on it when you could be doing somatic therapies [modification of the genome of an adult],? or developing treatments for rare diseases? I dont want to always assume the negative in the way I work.

Q. Do you think CRISPR will change the future of humanity?

A. Changing the genetic makeup of the population takes hundreds and hundreds of years. I dont think the birth of a quote-unquote successful baby using CRISPR technology will affect humanity. Were already mutating, so one more mutation I think we need to reflect on it, Im not saying ignore it, but lets not set our frameworks based on the worst case scenario, like, There should be a law against this " or other such instinctive reactions. We need a big public discussion, one that is not always based on the weird things that can happen.

Q. Do you have any red lines on genome editing?

A. I would put a red line against any type of editing that is not proven safe and effective before use in humans.

Q. But how does it prove that it is safe in humans?

A. Animal studies would have to be done.

Q. But at some point we would have to jump from monkeys to humans.

A. Yes, at some point, yes. When I started my doctorate, my first interview was with Patrick Steptoe and Robert Edwards, in Cambridge, after the birth of Louise Brown [in 1978, the first person born by IVF due to the work of Steptoe, a gynecologist and Edwards, a scientist]. Everyone was shocked talking of a slippery slope and the end of the world and saying the scientists were playing God. And now there are millions of children born through IVF who are totally normal and perfectly healthy. They are not monsters.

Q. The red lines are always moving. Did you have red lines 10, 20 or 30 years ago that you no longer have?

A. No, I have faith in people.

Q. In order to study how embryos develop, Spanish scientist Juan Carlos Izpisua and his team have created embryos made up of cells from both monkeys and humans. What do you think of this type of research?

A. It is one of the areas where species are being mixed. A man with a pigs heart genetically modified to be compatible has just died, for example. But these examples of xenotransplantation [transplant of organs from one species to another] are quite different from mixing human and animal cells in embryos. It is an area that disturbs me, but perhaps it disturbs me because I dont know enough about it. I think I need more information.

Q. Some scientists believe that these experiments with ape-human embryos are opening Pandoras box.

A. To say we are opening Pandoras box is to return to the accusations of the slippery slope and playing god. It is very easy to use these evocative expressions for political agendas, it doesnt help anyone to use this kind of language. Pandoras box opens, very well, and? What do we do or what do we not do?

Q. What is the moral status of an ape-human embryo?

A. I have no idea, maybe I could talk about their legal status, but the moral

Q. And the legal status?

A. There are all kinds of filters in the laws to distinguish between people and things or between people and animals. There are people who think that you only have to count the cells, to know how many belong to a monkey and how many are human. I do not believe that quantification can determine moral or legal status. We have to be very careful. We have always used animals for experiments, but we have never tried to transform animals into humans or vice versa. I think that would not be morally or legally acceptable.

Q. We can imagine a pig with a human liver, two human lungs and a human heart, but on the outside being a normal pig.

A. There are more than 100,000 people on the waiting list to receive an organ in the US, people who may otherwise die. If the animals are treated humanely, I think we should do xenotransplantation. Or, even better, why dont people donate their kidneys, if theyre going to die anyway? In some countries, like Spain, there is automatic organ donation, but even then the doctors ask the families. Why do you have a law if you ask the family later? Dont ask the family! It is legally accepted in a democratic society that organ donation is a good thing for all citizens, that they are humans helping other humans, and it is the law. Why not recover the organs in 100% of the cases? I hope to be able to donate all my organs.

Q. Your father was a Christian missionary. You said at a conference three years ago that you have been burned in hell many times. What did you mean?

A. I was at the Royal Commission on New Reproductive Technologies in Canada [created in 1989]. We listened to everyone and it was interesting, because a lot of religious extremists, anti-tech groups and extremist feminists came together with one position: that these technologies were morally wrong. So even though we had public sessions where everyone had a chance to speak, you were getting hate mail. They chose biblical language, like I should burn in hell, perhaps because they knew my father was a missionary. People can be quite cruel when they defend positions that they believe are morally justified.

Q. Do you still have problems with religious ideologies in your work?

A. Whether religious or not I find that extremist positions narrow my thinking, as if there were only one way of thinking and acting. They are practically anti-human positions, because they do not respect the beautiful complexity of human beings.

Q. One day in 2018 we learned that the Chinese scientist He Jiankui had created genetically modified babies. One morning will we find out that someone has cloned humans?

A. No, I think reproductive human cloning is one of the areas where there is almost universal consensus that we should never go down that road. It would create an element of industrialization in reproduction and turn people into things that can be copied. For me it is a red line.

Q. You dont like doing science fiction, but surely you can imagine that North Koreas dictator, Kim Jong-un, wants a copy of himself.

A. I find the idea that someone thinks they are so special as to think that there must be a copy of themselves so pathetic I dont think it will happen.

Read the original post:
Im disturbed by mixed monkey-human embryos, but maybe thats because I dont know enough - EL PAS in English

Margaret McGovern, MD, PhD, has been appointed deputy dean for clinical affairs at Yale School of Medicine and chief executive officer of Yale Medicine, effective July 1, 2022.

McGovern is currently Knapp Professor of Pediatrics and dean for clinical affairs at Renaissance School of Medicine at Stony Brook University and vice president of Stony Brook Medicine (SBM) Health System clinical programs and strategy. Prior to assuming these roles in 2018, she was chair of Pediatrics and physician-in-chief at Stony Brook Childrens Hospital. She led the development and planning of Stony Brook Childrens Hospital and markedly expanded its pediatric clinical research and education programs. McGovern also led the Stony Brook faculty practice plan for six years during her tenure as chair of Pediatrics. In 2019, she led the formation of the SBM Clinically Integrated Network, which is engaged in delivering high-quality, high value care by building a population health platform. She serves as the physician executive leader for the initiative.

She received her PhD in genetics from the Mount Sinai Graduate School of Biomedical Sciences and her MD from Mount Sinai School of Medicine (now called Icahn School of Medicine at Mount Sinai). She completed her residency training in pediatrics and fellowships in clinical and molecular genetics at Mount Sinai Hospital before joining the faculty. At Icahn, she was vice chair of the Department of Genetics and Molecular Medicine and professor of human genetics, and of oncological sciences and obstetrics and gynecology. She was the program director for the NIH-funded General Clinical Research Center (GCRC) and carried out CDC- and NIH-funded research focused primarily on the integration of molecular genetic diagnostic testing into clinical practice and inborn errors of metabolism. She is considered a world authority on sphingolipidoses.

At Yale, McGovern will play an essential role in the development of clinical strategy for the School of Medicine at an important juncture in the relationship between YSM and Yale New Haven Health System. She will provide strategic counsel and otherwise work to realize YSMs vision for its clinical enterprise. As CEO of YM, she will participate actively in the senior leadership group of the medical schools academic health system and play a key role in setting and realizing strategic goals. As deputy dean for clinical affairs, she will serve as the physician leader who represents the clinical mission of the School of Medicine in all venues. In this role, she will work closely with the clinical chairs in the recruitment of clinical faculty, mentor the next generation of clinical leaders, and collaborate with the deputy deans of research and education to balance the needs for enhancing the academic and educational missions of YSM with clinical ambulatory operational efficiencies, quality improvement, and sound clinical finances.

Submitted by Robert Forman on April 05, 2022

See the rest here:
Margaret McGovern, MD, PhD, Appointed YSM Deputy Dean and CEO of Yale Medicine - Yale School of Medicine

There are only a few thousand known cases of the condition of congenital insensitivity to pain worldwide. Picture courtesy of Natali Brillianata / Shutterstock via ETX Studio

PARIS, April 10 Patrice Abela first knew something was wrong when his eldest daughter was learning to walk and her feet left trails of blood behind her, yet she showed no sign of distress.

She was soon diagnosed with congenital insensitivity to pain, an extremely rare and dangerous genetic disorder that dooms sufferers to a lifetime of hurting themselves in ways they cannot feel.

Abela, a 55-year-old software developer in the southern French city of Toulouse, then watched in horror as his youngest daughter was revealed to have the same condition.

Now aged 12 and 13, the two girls spend around three months of every year in hospital.

When they take a shower, they perceive hot and cold, but if it burns they dont feel anything, the father of four told AFP.

Due to repeated infections, my eldest daughter lost the first joint of each of her fingers. She also had to have a toe amputated.

Repeated knee injuries have left both girls only able to move around using crutches or a wheelchair.

Abela said they may not feel physical pain but lamented their intense psychological pain.

Aiming to raise awareness about the disease and challenge the scientific community, Abela plans to run the equivalent of 90 marathons in fewer than four months. He plans to start on April 12, following the route of this years Tour de France from Copenhagen to Paris.

Danger everywhere

A life without pain might sound like a dream come true but the reality is more like a nightmare.

There are only a few thousand known cases of the condition worldwide. The low number is believed to be partly due to sufferers often not living into adulthood.

Pain plays a major physiological role in protecting us from the dangers of our environment, said Didier Bouhassira, a doctor at the centre for pain evaluation and treatment at Ambroise-Pare hospital in Paris.

In the most extreme cases, babies will mutilate their tongue or fingers while teething, he told AFP.

Then comes a lot of accidents, burns, walking on fractured limbs which heal badly, he added.

They have to be taught what is innate in others: to protect themselves.

But when there are no warning signs, danger lurks everywhere.

Appendicitis, which announces itself in others via symptoms like pain and fever, can fester into a devastating general infection of the abdomen.

Blindness can also occur because the eye must always be kept moist and the nervous system controls these processes via the so-called blink reflex, said Ingo Kurth of Germanys Institute of Human Genetics.

New painkiller hopes

Congenital insensitivity to pain (CIP) was first recognised in the 1930s, and numerous studies have since identified a genetic mutation that blocks a persons ability feel pain.

We have learned that there are now more than 20 genetic causes of congenital or progressive insensitivity to pain, Kurth told AFP.

There is no cure and no real drug breakthroughs have been made so far, Kurth said.

But our understanding of the molecular causes of CIP continues to reveal new targets, and based on this, hopefully new therapies will be developed in the coming years.

There are also hopes that studying how CIP works could lead to the development of a new kind of painkiller, prompting huge interest from pharmaceutical giants seeking a fresh product in the billion-dollar industry of pain relief.

In this way, the unlucky few with CIP could contribute to the creation of a treatment that would help everyone in the world except themselves. AFP

See the article here:
The suffering of those who cannot feel pain - Malay Mail