Who Owns the Moon?

 Who is the official owner of the Moon?

While United States astronauts were the first to visit the Moon, this does not mean that the United States owns it. In fact, under the 1967 Outer Space Treaty no country has a unique ownership in the Moon and all nations are accorded equal rights and access.

An Interview with Space Law Expert — Prof. Frans von der Dunk

Joel Cohen (Host): Let's talk a little bit about our closest neighbor the moon. First off, who owns it and who has a right to access it or exploit it?

Ownership of the moon

Professor Frans von der Dunk: The easy answer is, nobody owns it, or more correctly the whole community of states owns it together. Because if you say that nobody owns, it leaves open the possibility for someone to step in and say “from now on, I own this part” and that is a no-go area. The Outer Space Treaty, the most important treaty in outer space, agreed upon in 1967 between all important space faring countries, agreed that no state could ever appropriate part of the moon.

Host: Did the Outer Space Treaty call for any type of supranational authority to regulate that or is it still on the state-by-state level to make sure that they're in compliance?

Prof. von der Dunk:  They didn't call for an international authority in the sense of an international organization or body. The international authority, if you will, is international law as such, but the international law consists of treaties to which sovereign states decide whether they want to adhere or not. The Outer Space Treaty is the prime example of such a treaty, and by that token they did agree on a number of rules of the road. But it's not like there is any organization whether it's the United Nations or anyone else ruling that area. And in that sense, it's basically like the high seas. It is often referred to as a global commons which means that it's open to all states as long as they comply with existing international rules to to use it, to explore it, to exploit it to the best of their abilities.  And there's no single state which can stop that from happening for another state.

 

Can nations set up bases on the moon?

Host: So, if no one owns it and everyone owns it, practically what would that mean for a nation or a company that wanted to set up a base or a headquarters on the moon?

Prof. von der Dunk: Well that's a great question, and on the face of it, it is open. Now let me premise this by saying that there you have to make a difference between a private company and a state. The freedom of space activities like there is a freedom of activities on the high seas is open for states in principle in first instance only and private sector operators depend upon the authorization of their state whether they can enjoy that freedom as well. And if they do, the states are responsible and liable for what they do out there so in that sense there is a basic freedom for outer space activities. The problem with the exploitation of mineral resources on the moon or other celestial bodies which are legally speaking in the same basket (so obviously there are major differences between the moon and mars or a small asteroid but in legal terms they're all the same) and if you want to exploit them the only rule which is there is that it says you can't carve out a part of that area as a country and say this is ours and everybody else has to stay out, or only is allowed to get in under my permission. That is a no-go, but whether that means that you can actually allow private operators to go there and mine, that is at least politically still an open question because the outer space treaty didn't really solve that simply because it was not on the agenda in 1967.

 

The Moon Agreement

Host: You mentioned the oceans as an analogy. I understand that when it comes to mining in the oceans, there is a treaty that allows certain countries to apply for and receive mineral rights. I understand the United States is not a part of it, but there's no such analogous agreement on the moon, am I correct?

Prof. von der Dunk: You're absolutely correct. There was an effort to create an analogous regime back in 1979 with the Moon Agreement but that is not ratified by almost all of the major space faring countries, not just the United States but also Russia and China and all the major other ones are not party to that. So, we can safely ignore it at this stage. So there is no comparable regime, so it's a little confusing.
 

A Right to Access on the Moon

Host: Let's say I want to set up my headquarters on the moon and I represent Botswana. Let's take all the practical implications out and all the costs out. Would that mean that the United States could then come onto my lunar compound and set up a building right in the center of it and say, look, you don't own this land, we all do.

Prof. von der Dunk: The first part of the answer is yes, they can come in – at least duly authorized representatives of the United States can come in to basically to check and see whether Botswana is up to any violation of the requirements applicable to the moon in terms of no military establishment, no weapons, and things like that. On the other hand, Botswana has the right to take reasonable precautions and say okay you have to give us a few weeks to make sure that everything is safe here. You can't just barge in like that, again practical things put aside. The United States certainly cannot say well we're going to occupy your building. So the freedom of outer space activities means explicitly that you can build stations on the moon. You can even take reasonable precautions as I said before. You have to allow others in and the fact that you are able to build a station on the moon does not mean that you own that part of the moon forever and ever. So, if you at some point in time do not continue operations there and you let it fall apart, then after probably just a few years, there is no consensus on this yet, but that's the kind of rules that we need to develop.  But maybe after a few years somebody else can come in and say well this is a ruin. This doesn't belong to anyone really anymore. Botswana has long given up on this. Now I’m entitled to build my own thing here.

Host: Is this some type of lunar squatter's rights or adverse possession?

Prof. von der Dunk: Yes, with the limitation that when we use those terms in U.S. law, of course, it brings in a whole host of quite specific obligations and rights because in the U.S., we've been working with these terms for centuries almost, and the courts have by now very precisely carved out what they mean and what they do not mean, et cetera et cetera. Of course, we can't just transplant U.S. law and U.S. jurisprudence to the moon precisely because the moon is not part of the United States. So the best we can say is that to the extent that there is a common denominator between this U.S. system and other major legal systems in the world, many of which have something somewhat similar, to the extent that there is this common denominator that would apply and actually that is reflected, if you will, by these clauses in the Outer Space Treaty, which say you can't own the land, but you're free to use it.  The fact that you can't own it means that at some point in time, you can't keep others off. You can't keep everyone out forever. Now whether that means that you can continue to use that place forever and thereby de facto keep everyone out is still an open question. And if you allow me to draw a kind of a parallel in terms of satellite communications, we have now agreed that 25 years of occupying one particular orbital slot in the geostationary orbit is about right.  But once that period is over, in principle, that slots should revert to the open pool. It might be that others are entitled to replace that slot so that's kind of the timelines that we are thinking about.

 

Safety zones on the moon

Host: In terms of some type of buffer zone, if we return to the analogy of the ocean, there are U.S. territorial waters that go out a certain number of miles. Would there be some type of buffer zone around your little space station that would be reasonable for safety reasons or reasonable for privacy reasons?

Prof. von der Dunk: Yeah reasonable is a dangerous legal term of course, and it is not mentioned in the Outer Space Treaty. It just talks about reasonable precautionary measures. So there you find actually the word “reasonable” referenced. The idea of a zone as such is not mentioned partly because of the fear that that might ultimately somehow spill over into territorial possession because it may give a sense that I own whatever is in the zone that I can completely dictate what's going on there that I treat that as part of my own territory. That was to be prevented. On the other hand, if you announce a safety zone and it is a reasonable precaution so it shouldn't be 20 miles but if it's say 150 meters, that's reasonable. And if you tell everyone if you come within that zone without prior information, without announcing that, you're acting in a way that may endanger our operations, then we feel ourselves entitled to see this as enemy activity or as a dangerous activity. And we feel entitled to act accordingly. That's the political situation where we are. This is not legally sought out so what legally becomes important is the moment that somebody officially announces a safety zone like that, how do other states react? Do they think, yes it's perfectly reasonable to announce a safety zone of half a mile just to quote a number and actually we are going to do that ourselves. Then before you know it, you have customary international law that a safety zone of half a mile is very reasonable. If, by contrast, everyone would fall over that first state and say that's ridiculous, that's a violation of Article 2 of the Outer Space Treaty and of other rules, then probably the first state must gradually withdraw unless it really wants to fight for it, which we're not hoping for in outer space obviously but that's kind of the legal tension we are talking about.

Credit: Talks on Law.com

A gene editing technique shows promise for lowering LDL cholesterol

 

PHILADELPHIA ­— Ten patients enrolled in the experimental drug trial, and they were the sickest of the sick. 

All had a genetic disorder that cranks up levels of LDL cholesterol in the blood. Known as “bad cholesterol,” LDL cholesterol is infamous for clogging arteries. The patients’ disorder, called heterozygous familial hypercholesterolemia, can lead to severe heart disease at an early age — and death. 

Their arteries had been bathing in high LDL cholesterol since birth. In several patients, even typical cholesterol-lowering drugs couldn’t get the levels “even remotely under control,” says Andrew Bellinger, a cardiologist and chief scientific officer at Verve Therapeutics, a Boston-based biotechnology company.

Now, his team has tried a new approach: a genetic medicine called VERVE-101 designed to turn off a cholesterol-raising gene. Using a kind of molecular pencil, the medicine erases one DNA letter and writes in another, inactivating the gene. A single genetic change. A single medication. A potential treatment that lasts a lifetime.

That’s the hope, anyway. Bellinger presented the results of a small clinical trial called heart-1 at the American Heart Association meeting in November. VERVE-101 successfully lowered LDL cholesterol, Bellinger reported. It’s the first time anyone has shown that a DNA spelling change made inside a person’s body could have such an effect. “We can achieve clinically meaningful LDL reductions with a single dose,” he said.

Now, his team has tried a new approach: a genetic medicine called VERVE-101 designed to turn off a cholesterol-raising gene. Using a kind of molecular pencil, the medicine erases one DNA letter and writes in another, inactivating the gene. A single genetic change. A single medication. A potential treatment that lasts a lifetime.anyone has shown that a DNA spelling change made inside a person’s body could have such an effect. “We can achieve clinically meaningful LDL reductions with a single dose,” he said.

People with familial hypercholesterolemia have lifelong symptoms, so “this whole concept of ‘one and done’ is really amazing,” says Pam Taub, a cardiologist at the University of California, San Diego who was not involved with the trial. These patients must take medications their entire lives. An infused drug like VERVE-101 — designed to alter a person’s DNA — could change treatment strategy. 

Taub points out questions about VERVE-101’s safety. One trial patient had a heart attack. Another died due to cardiac arrest. But that death was not related to treatment, Bellinger said.

Moving forward, establishing VERVE-101’s safety is crucial, agreed Karol Watson, a cardiologist at the David Geffen School of Medicine at UCLA who wasn’t involved with the new work. Editing people’s DNA to lower their cholesterol “is a strategy that could be revolutionary, but we have to make sure it’s safe,” she said at the meeting. “You are changing the genome forever.”

Here’s what we know about four key aspects of the new medicine and its history.   

VERVE-101 relies on a DNA-modifying protein called a base editor  

The composition of VERVE-101 is simple. It’s just two types of RNA molecules — molecular cousins of DNA — bundled inside a bubble of fat. 

Infused into the bloodstream, the drug travels to the liver and slips into cells. One of the RNA molecules tells cells to build a protein called an adenine base editor. The other acts as a genetic GPS, guiding the editor protein to the correct stretch of DNA

The technology is CRISPR 2.0. First generation CRISPR/Cas9 tools act like molecular scissors and can disrupt genes by snipping through DNA’s strands (SN: 8/14/19). Base editors are more like molecular pencils. They edit DNA by performing chemistry on an individual DNA letter, or base, rewriting for another  creating a new genetic sequence

“Base editors actually change a sequence that you choose into a different sequence of your choosing,” says Howard Hughes Medical Institute investigator David Liu, a chemist at Harvard University whose team [nvented technology in 2016 In the case of VERVE-101, that sequence is inside the PCSK9 gene, which encodes instructions for manufacturing a protein that raises blood cholesterol levels. Just one edit in a precise location shuts PCSK9 down.

Editing wraps up less than a week after the infusion, and the drug breaks down rapidly, Bellinger said. Both the fat bubble, called a lipid nanoparticle, and its RNA cargo degrade, and within a few weeks, VERVE-101 vanishes from the body. “The only thing that’s left is the DNA change you made to the PCSK9 gene,” he said.

PCSK9 is a tempting target for gene-editing therapy 

PCSK9 has been a hot therapeutic target for the last decade or so, says Parag Joshi, a preventive cardiologist at UT Southwestern Medical Center in Dallas who was not part of the trial. 

Researchers knew that some people have PCSK9 mutations that switch the gene off. These people tended to have lower levels of LDL cholestrol and drastically have less heart disease geneticist Helen Hobbs, an HHMI investigator at UT Southwestern Medical Center, and colleagues reported in 2006.

That landmark study pushed the field forward, Joshi says. Suddenly, scientists had proof that people could live healthy lives when PCSK9 was inactivated. That made it “a very attractive drug target,” Joshi says. It suggested that disabling PCSK9 would do no harm — and could even help, by lowering the risk of heart disease.  

Typically, the PCSK9 protein breaks down another protein called the LDL receptor. This receptor is one of the good guys; it keeps bad cholesterol in check by snatching it from the blood and transporting it into liver cells for disposal. Without enough LDL receptors, LDL cholesterol levels in the blood ratchet up.

 

Sekar Kathiresan, a cardiologist and Verve’s CEO and cofounder puts it succinctly: PCSK9 causes disease. “If you turn it off, all you get is health.”

Today, a few existing therapies target PCSK9, including injected antibodies or an RNA-based drug that shuts down production of the protein. Patients should take a daily statin pill to lower LDL cholesterol, Joshi says. But it’s often not enough. 

And though the therapies are theoretically effective for people with familial hypercholesterolemia, Kathiresan says, “very few patients are actually on these medications.”

His team thinks that’s because the current approach is just too heavy a burden — asking patients to take daily pills or intermittent injections for decades. “That model doesn’t seem to be working,” Kathiresan says. “And that’s what we’re trying to fix.” 

Early VERVE-101 clinical trial results reveal potential benefits — and risks 

Kathiresan’s team gave a single IV infusion of VERVE-101 to 10 people with heterozygous familial hypercholesterolemia, most of whom had severe heart disease. In those who received the highest drug doses tested, blood levels of LDL cholesterol dropped sharply, by 39 to 55 percent. And the drop appears long-lasting, Bellinger said. For the patient at the highest dose, LDL cholesterol levels held steady for 180 days after VERVE-101 infused into the bloodstream.

Steep reductions

In a clinical trial with 10 participants, people who received the highest doses of VERVE-101 tested (green and purple dots) saw steep reductions in the amount of LDL cholesterol in the blood.

Changes in LDL cholesterol levels for different doses of VERVE-101

Dosage (mg/kg)

0.1

0.3

0.45

0.6

Source: S.B. Vafai et al/American Heart Association meeting 2023 • Visualization: C. Crockett

Bellinger called the results “pretty much what we expected and planned,” given the team’s earlier result in nonhuman primate.   But the new patient data, though preliminary, places the drug on the precipice of something bigger. “This opens the door for an entirely new way to treat heart disease,” Kathiresan says.

VERVE-101’s utility will ultimately depend on its safety. During the trial, the team spotted some potential red flags. Four patients had minor reactions to the IV infusion, including headache and mild fever. But at the heart meeting, attention hummed over something more severe. A day after the infusion, one patient had a heart attack. Five weeks after the infusion, a different patient died when their heart suddenly stopped beating. 

That incident was probably caused by the patients’ underlying heart disease, Kathiresan says. That’s the conclusion reached by an independent data safety monitoring board that investigated the cases, he says. 

The heart attack, however, may have been related to the treatment, because it happened so soon after dosing, the monitoring board determined. Kathiresan notes, though, that the patient had been experiencing chest pains prior to the study, something they didn’t mention to the study’s investigators.

These are “very, very sick patients,” says UCSD cardiologist Taub. For future trials with the drug, she thinks such patients should be excluded.

Kathiresan’s team is now planning to enroll patients with less-advanced disease. They’re also going to check for blockages in patients’ arteries, to try and avoid including people at extremely high risk of heart attack.

In 2024, the company plans to enroll more patients at the two highest doses to determine which dose to move forward. The researchers are also testing a second version of the drug, VERVE-102, which uses a different lipid nanoparticle. Depending on those results, Verve plans to move one of the drugs on to a larger clinical trial in 2025. And if successful in people with familial hypercholesterolemia, the company intends to expand to an even broader group of patients, including those without the genetic disorder.

Developing new medicines is a long road, Kathiresan says. It can take more than a decade for a drug to go from a concept to a medication that doctors can prescribe, he says. Verve started its PCSK9-editing project in 2018. Kathiresan says he hopes to have an approved medication by the end of the decade. 

VERVE-101 is one of several base editing drugs currently in clinical trials

One potential side effect of gene-editing therapies is unintentional tweaks to DNA. VERVE-101 targets PCSK9, but what if it strays to a different spot in the genome, asks Anne Goldberg, an endocrinologist at Washington University School of Medicine in St. Louis. The technology “looks really interesting,” she says, “but we need more data.”

A DNA change at the wrong spot could put people at risk of developing cancer. With VERVE-101, Bellinger said, “we think that risk is very low.” Most of the company’s work, he said, goes into demonstrating that “we do not make edits elsewhere in the genome.” 

Today’s base editors — including the one in VERVE-101 — are much improved since the early days of the technology, says Harvard’s Liu, who was not involved with the trial. They “have very high on-target editing efficiency while also having minimal off-target editing.” 

Currently, five other base-editing clinical trials targeting other diseases, like sickle-cell disease and leukemia, are ongoing. Liu is hopeful that the gene-editing agents will give patients “a completely new lease on life.” 

Bellinger said his team thinks of VERVE-101 as a one-time procedure for health, like “molecular surgery without a scalpel.” In theory, it’s possible to reverse the edit made by VERVE-101, but it’s not what he and his colleagues envision. 

For cardiologist Donald Lloyd-Jones, who was not involved with the trial, the dream is to offer people with familial hypercholesterolemia a treatment that doesn’t rely on taking a statin pill every single day. A therapy like VERVE-101 “might be something they really consider as an option,” said Lloyd-Jones,

Currently, five other base-editing clinical trials targeting other diseases, like sickle-cell disease and leukemia, are ongoing. Liu is hopeful that the gene-editing agents will give patients “a completely new lease on life.” 

Bellinger said his team thinks of VERVE-101 as a one-time procedure for health, like “molecular surgery without a scalpel.” In theory, it’s possible to reverse the edit made by VERVE-101, but it’s not what he and his colleagues envision. 

For cardiologist Donald Lloyd-Jones, who was not involved with the trial, the dream is to offer people with familial hypercholesterolemia a treatment that doesn’t rely on taking a statin pill every single day. A therapy like VERVE-101 “might be something they really consider as an option,” said Lloyd-Jones, of Northwestern University Feinberg School of Medicine in Chicago.

“If we get those safety data, if we get those efficacy data,” he said at the meeting, “I think this would be a very interesting approach to a lifetimetoday fix. 

”Source: Science News