Lifeboat Foundation: Safeguarding Humanity
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Category: biotech/medical – Page 2,041

Gene editing of human embryos — yes or not?

If there is a discernible duty here it is surely to create the best possible child. That is what it is to act for the best, all things considered. This we have moral reasons to do; but they are not necessarily overriding reasons.

Steven Hawking initially predicted that we might have about 7.6 billion years to go before the Earth gives up on us; he recently revised his position in relation to the Earth’s continuing habitability as opposed to its physical survival: “We must also continue to go into space for the future of humanity,” he said recently. “I don’t think we will survive another thousand years without escaping beyond our fragile planet.”

We will at some point have to escape both beyond our fragile planet and our fragile nature. One way to enhance our capacity to do both these things is by improving on human nature where we can do so in ways that are “safe enough”. What we all have an inescapable moral duty to do is to continue with scientific investigation of gene editing techniques to the point at which we can make a rational choice. We must not stop now.

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In October 2019, Liu and his colleagues published a paper in Nature, describing an even newer technology, called prime editing. Prime editing can not only make all twelve of the possible base substitutions, it can also make multiple-base insertions or deletions, without requiring a double-strand break. It achieves this with a multi-step operation that first cuts one strand, then performs the appropriate substitution, insertion, or deletion, and then nicks the second strand to allow the bases on the second strand to be replaced by bases that complement the ones substituted, inserted into or deleted from the first strand. The result is a modified stretch of DNA that had never been completely separated. This has the effect of massively reducing the number of off-target modifications.

This new prime editing variant of CRISPR technology, can make the same corrections to the defects that cause sickle cell disease and beta-thalassemia that standard CRISPR/Cas9 has now made in human subjects, but with less opportunity for unwanted off-target changes. Furthermore, its possible applicability is much wider. The ClinVar database lists over 75,000 pathogenic mutations in the human genome. Of these, over 89% are potentially correctable by prime editing.

From zinc fingers to TALE, to CRISPR/Cas9 to base editing and now to prime editing, progress in gene editing has been accelerating. The next advances are currently being aggressively pursued in laboratories all over the world. It will probably be several years before the therapies that are currently being researched are applied routinely in a clinical setting. However, for people who up until recently have had no hope for a cure to a disease suffered by their child, or even themselves, these are exciting times. The prospect of effective treatments, or even cures, is now a valid cause for hope.

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The Human Genome Project is probably the most ambitious scientific proposal ever made.

ii. writing DNA

Synthesising short, single stranded fragments of DNA, called oligonucleotides (oligos for short) has been automated and affordable for a number of years now, and almost every biology laboratory in the world uses these short fragments (usually 18–25 base-pairs — compare this to the human genome which is 3 billion base-pairs long) for applications ranging from disease diagnostics to making genetically modified plants. What really has been a game-changer in DNA synthesis is the ability to synthesise longer pieces of DNA and the ability to join these together efficiently to form synthetic gene length fragments.

This ability to synthesise DNA quickly and cheaply has excited a group of biologists who want to use it to create entire genomes from scratch. To study life by building it, gene by gene. Going further, scientists want to create a “minimal genome” to identify exactly only those genes absolutely necessary to support the most basic form of life. Genome synthesis could also enable us to create optimised strains of biological workhorses like yeast, to more efficiently produce pharmaceuticals and fuels. These ambitions have fuelled the field of synthetic genomics, beginning with the synthesis of a Mycoplasma mycoides genome by Craig Venter in 2008.

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How close are we to creating a synthetic human genome?

Creating humans is also an ethical minefield. Unsettled questions about who might own a synthetic human genome abound. Boeke warns that ownership could come down to who ends up funding the project development. Rob Carlson, a co-author of the GP-Write proposal, is even more skeptical of the idea of a patented artificial human genome, pointing out via email that “as soon as there is any possibility of a synthetic genome being used to germinate a live human, then ownership is obviously out of the question anyway…because you are now talking about owning a person.”

So far the GP-write project has been more talk than action, with large consultation meetings held between scientists and policy experts. The project has yet to attract significant funding. Perhaps successes in other organisms like yeast will embolden governments and private industry to open up to the idea of a man-made human genome.

Given that building a genome is so technically demanding, and with uncertain rewards, I’ve often wondered why anyone might want to undertake such a venture. Some, like Boeke, seem to be in it mainly for the science — for the questions that can only be answered by building life from scratch. Others, like Harvard geneticist George Church, a genome sequencing pioneer and co-author of the GP-write proposal, are more excited by the potential life-changing applications. In any case, it’s clear that writing genomes is the next major scientific frontier — and that we’re well on our way to crossing it.

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Newborn screening covers more than 30 conditions. Yet, with genome sequencing, we could screen newborns for several thousand genetic conditions.

In the surveys’ open-ended responses about risks of genome sequencing, parents and clinicians both expressed concerns about psychological distress related to difficult or uncertain results. Clinicians were more likely to raise concerns about returning results for adult-onset conditions, unnecessary parental stress over health problems that might never actually occur, and the possibility of future discrimination against the child on the basis of their genomic information.

On the other hand, parents mentioned a broader range of benefits than clinicians. Both parents and clinicians saw potential health benefits of genome sequencing, such as the ability to search for more conditions compared to standard newborn screening and the ability to predict a child’s future disease risks. Parents went further, though, seeing benefits in family planning, preparing for the child’s future, and knowledge just for the sake of knowing. Those potential benefits fall outside of traditional definitions of clinical utility, which means they are less likely to be considered in the professional guidelines that steer adoption of practices like genome sequencing.

This brings us into a debate that may be central to the near future of genome sequencing, not only for newborns but for ostensibly healthy adults as well: how to define the utility of genomic technologies. How much weight, if any, should patients’ perceptions carry? If they think genomic information will have utility, should that count for something, even if clinicians and researchers have their doubts? Should the idea of “clinical utility” be expanded beyond information that directly affects medical care, perhaps including perceived quality of life impacts for patients?

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BEIJING—Clinical trials being conducted in Wuhan to test Gilead Sciences Inc.’s antiviral drug, a promising remedy for the new coronavirus, are going more slowly than hoped for as the drugmaker struggles to recruit qualified patients, underscoring the challenges in quickly developing drugs during outbreaks.

The trials, aimed at testing more than 700 patients infected with the Wuhan coronavirus, have succeeded in recruiting fewer than 200 people after 10 days.

A total of 168 patients with severe symptoms, and 17 patients with mild and moderate symptoms, were recruited at 11 medical institutes across Wuhan, Zhang Xinmin, an official from China’s Ministry of Science and Technology, said at a Saturday press conference.

https://www.wsj.com/…/gileads-coronavirus-drug-trial-slowed…

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At some point in their life almost everyone will develop a cavity in their teeth and about 70% of the global population will experience varying degrees of gingivitis. Regular brushing is the best way to prevent dental disease, but sometimes that is not enough as microscopic plaque can be left behind after brushing your teeth.

According to the Health 2000 Population Survey over half of Finns aged 30+ suffer from gum disease; and research indicates that undetected oral and chronic infections can contribute to the occurrence of many diseases such as cardiovascular disease, diabetes, and lung cancer as well as increasing the risk of premature delivery.

Aalto University and Helsinki University Hospital researchers have founded Koite Health which is launching a method for home use in the coming weeks that can kill streptococcus mutans bacteria as well as the bacteria that can cause gingivitis, which has been shown to reduce the markers indicating early gingivitis and plaque formation.

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James W. Clement is a longevity researcher who was the 12th person on the planet to have his DNA sequenced. In 2010 James launched his Supercentenarian Research Study, which he started in 2010 with Professor George M. Church of Harvard Medical School. Since then Clement has read 20,000 medical research papers on longevity and has acquired one of the largest DNA databases of supercentenarians, the youngest of whom is 106 years old. Most recently James W. Clement is the author of the Switch: Ignite your metabolism with intermittent fasting, protein cycling, and keto. Finally, I know James personally and have gone to visit his previous research lab in Apple Valley, California, so I can honestly say that he is among the most humble humans and the hardest-working longevity researchers that I have ever seen. I have learned a lot from Clement and I hope you do too.

During this 2 hour interview with James W. Clement, we cover a variety of interesting topics such as: Clement’s journey from being a lawyer to becoming a full-time longevity researcher; the name and story behind Better Humans; why James is a transhumanist; why we have to first make it to 100 before we start taking “magic pills”; the switch between mTOR and autophagy; the importance of intermittent fasting, its time and duration; the connection between gut bacteria and dopamine; why the biggest problem of our diet is the overconsumption of both dairy and meat; protein cycling and why we can’t sustain autophagy indefinitely; the dangers of coconut oil; why all centenarian blue zones in the world eat high-carb diets and why we should try keto.

My favorite quote that I will take away from this interview with James W. Clement is:

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Magnetic resonance imaging is no longer confined to radiology departments. The U.S. Food and Drug Administration announced Wednesday that it has provided clearance to the “world’s first” bedside MRI system, according to an announcement.

Hyperfine said it will begin shipping its portable, low-field modalities this summer. It’s 510(k) clearance falls on the same day that Yale researchers reported the device can accurately and safely image patient’s brains for stroke. Those preliminary results are set to be presented next week at the American Stroke Association’s International conference in Los Angeles, the group announced.

“We’ve flipped the concept from having to get patients to the MRI to bringing the MRI to the patients,” said Kevin Sheth, MD, senior author and a chief physician at Yale School of Medicine. “This early work suggests our approach is safe and viable in a complex clinical care environment.”

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