SAVING COVID‑19 PATIENTS, IN FRANCE, RIGHT NOW! THE RESOURCES OF THE SEA Dr. Franck Zal, a former CNRS (French National Centre for Scientific Research) researcher, CNRS Bronze Medalist, and CEO of the marine farm and SME "Hemarina" since 2007, has developed an oxygen carrier, today used in transplants that should urgently be used for clinical trials on COVID‑19 cases.

Dr. Franck Zal

Question: You come from marine biology research to propose new therapeutic methods? Dr. Franck Zal:

Indeed, as a researcher at the CNRS, I conducted research in marine animal physiology, and particularly in ecophysiology, for close to 15 years, bearing notably on the marine worm - Arenicola marina - which has existed for 450 million years on earth. This marine worm has a special extracellular haemoglobin protein that enables it to carry 40 times more oxygen than human haemoglobin (160 molecules instead of only 4). Besides, this molecule has no blood typing. De facto, it is the ancestor of our red blood cells!

The molecule acts as an "oxygen bottle" which allows the worms to survive in extreme conditions during low/high tide changes. I proposed to the CNRS to develop this research for products to treat human pathologies, but the CNRS just advised me to sell my discoveries to a private company. Being involved in public research, I was shocked and therefore resigned to create my own enterprise, Hemarina, in 2007, in Morlaix, Brittany.

Ferme marine de Hemarina

Our approach is part of biomimicry. For instance, take a transplantation case, when the surgeon removes a graft, the organ will deteriorate very quickly due to the lack of vital oxygen delivered by the blood circulation. What happens if I put this molecule in the organ preservation solutions ? The life span of a lung, 6 to 8 hours is increased to 48 hours with our molecule ! The organ has now access to a physiologic oxygen stock. We have also developed oxygenating dressings to increase the speed of healing, as well as products to treat periodontitis that do not require the use of antibiotics. In Hemarina, we set up a technological R&D platform offering a wide range of applications. Oxygen is essential to life and our molecule is able to oxygenate cells, tissues, organs and entire organism. Applications are wide indeed.

Oxygen is essential to life and our molecule is able to oxygenate cells,

tissues, organs and entire organism.

Question: And now you come to COVID‑19 with concrete proposals in view of data showing the effect of the coronavirus on the blood ? Dr. Franck Zal:

Indeed, I have a few thousand doses available, originally dedicated to be used in a clinical study in France and also to be provided to transplant professionals in India. Then, I decided to , freeze this stock when I was asked to provide HEMO2life as a potential therapy for some COVID‑19 patients in FRANCE!

Hemarina has an Arenicola marina farm in Vendée to ensure its raw material procurement. Our technology is now successful and has a worldwide reputation. Everyday we are contacted by a lot of health professionals worldwide for ischemia and/or anemia issues. Prof. Lantieri, who knows well the contribution of this product for his transplants, contacted me: "The coronavirus is like a Tsunami, would you be willing to help?

Because the evolution in the understanding of the coronavirus, from scientific studies and autopsy reports, are now piling up, and indicate that COVID‑19 is a disease affecting oxygenation in humans result being a severe hypoxia. Since April 8, when our first COVID‑19 trial was due to start, we have, globally, discovered even more facts about coronavirus disease that show it is more than just a respiratory syndrome. As illustrated by a publication in The Lancet, and reports of high mortality rates in US, COVID‑19 is a hypoxia problem.

However, a lot of doctors seem to have left behind pathophysiology classes: “When we put classic oximeters to our patients, oximeter readings are not correct” “Of course” I would say because “oximeters are calibrated for functional red blood cells. Their molar extinction coefficient is subject to modification in case of COVID‑19”.

COVID‑19 appears to be a disease of the ventilatory system (pulmonary gas exchange...) and circulatory system (oxygenation, coagulation...) which will create a generalized hypoxia and will lead to a multi visceral failure. Given the problems of intubation in Acute Respiratory Distress Syndrome (ARDS) as detailed by a world expert Prof. Luciano Gattinoni, it would be really important to see if we can act directly on oxygenation. A few days ago, out of more than 2,500 patients, 9 out of 10 on ventilation died in New York! The hemoglobin of the arenicola worm could therefore help solve the problems of micro-thrombosis and oxygen supply. We obtained the authorization from the ANSM (France’s National Agency For Medicine Safety) on April 8, and from the CPP, the Committee for the Protection of Persons, which gave its green light.

But since the original trial was suspended on April 8 (there had not yet been any inclusion) on the basis of totally false claims – since it was not at all the same product – we have linked with other anaesthesiologist teams interested.

Question: So you're waiting for a new clinical trial?

Dr. Franck Zal:

With Laurent Lantieri, we have been working hard to set up a protocol and develop a proposal for a clinical trial using our oxygen carrying molecule. My opinion is clear: "Let's be pragmatic: let's apply war time medicine. »

But in addition to that, I must say that we have had disputes with the administrative authorities, particularly with the APHP (Paris Hospitals Authority), which would like us to hand over the property rights on our products, and then wanted to be paid royalties. In my opinion, the APHP behaves as a "manager" and not as a representative of healthcarers and patients!

On the contrary, I propose an Open Source use of our products. I give it away! My only wish: that we save lives in France! We have therefore made contacts in the East of France to redo a clinical protocol, which is currently underway.

Questions: What about the use in other countries? India, African countries? Are they interested in carrying out clinical tests?

Dr. Franck Zal:

The medical centres aboard, on the other hand, want to test the molecule. I'm inundated with requests from India, Mexico, the US, China and Italy. But I have to confess, I must be a bit foolish as I was hoping that our French invention could save lives in France first! We have some doses in stock, in case, we can quickly go to 15 000, and at a rate of 5 vials per patient, we could save a few thousand human lives, here, right now. The arenicola marine worm has an extracellular hemoglobin, not typed (so it is a universal donor)!

Question: If we think of Martinique, Guadeloupe, and of course African countries, there is the genetic sickle cell disease, which is characterized by inefficient hemoglobin. Do you think that therapeutic applications are possible?

Dr. Franck Zal:

Indeed, in the case of sickle cell disease, the red blood cells are sickle-shaped and cannot carry oxygen. Blood clots, cramps, organ deficiencies, etc. are observed in patients. Our molecule developed being 250 smaller than red blood cells, and 40 times more effective than human hemoglobin, can quite therapeutically be used to treat these symptoms.

Question: Japan has a lot of ventilators: 111 machines per million people. By way of comparison, France has only 20 per million! So the Japanese rely on their technological strength, but here as elsewhere, there is no taking a step back.

Dr. Franck Zal:

Some practitioners find that intubation with ventilators can have perverse effects. Taking a step back is indeed essential, especially if the problem is the lack of capacity of the hemoglobin which allows the transport of oxygen in the body! Once again, we must explore all the therapeutic possibilities to save lives. I'm not saying we have the miracle solution, I'm saying we need to start clinical trials NOW, urgently.

Interview by Arno Germond and Garance Upham,

AMR Think-Do-Tank, International Geneva

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