Protein FAQ

Algae are photosynthetic aquatic creatures that grow through the consumption of nutrients, light, and carbon dioxide. They are a diverse group of creatures that include tiny single-celled algae and enormous kelp, as well as seaweed 1. Numerous prokaryotic and eukaryotic algae species are desirable food sources for humans due to their inherent qualities 2,3. Human intake of macroalgae such as seaweed and microalgae like phytoplankton dates back many years. Multicellular macroscopic aquatic plants, or macroalgae, are classified into three taxa: Phaeophyceae, or brown algae, Rhodophyta or red algae, and Chlorophyta or green algae. Microalgae, the unicellular counterpart of macroalgae, are categorized in a broader framework that includes prokaryotic cyanobacteria (blue-green algae), Euglenophyta, and Chlorophyta, which are genetically distinct from one another. The ancient populations of Chad and the Aztec culture were already familiar with the cyanobacteria spirulina, which is currently advertised as a superfood in the West 4. In Burma, Vietnam, and India, other cyanobacteria/microalgae, like Spirogyra and Oedogonium, were eaten as food or as a supplement 4. Seaweed is a staple of daily meals in many Asian and Pacific civilizations, including Korea, Japan, and Indonesia, as well as Hawaii and New Zealand 5.

You're average biomedical researcher is dealing with a huge amount of new information every day. You're getting over 10,000 new publications uploaded on a daily basis worldwide across all the biomedical journals and databases, so there is no way that one researcher can actually even access, let alone read all these huge amounts of data. What we have to do is use deep learning to be able to help us ingest all that data and do some initial deep triage of that data to surface new therapeutic opportunities. It’s meant to provide insight for our biologists and chemists, so they can actually deal with a usable amount of information.

There are no targeted treatments approved for pancreas cancer, and we haven't had any significant progress for a long time. We've only come up with different chemotherapy combinations, and those are only moderately effective. This new treatment is staggeringly better than chemotherapy. Usually, when we think of an improvement in pancreatic cancer survival, we think of 25% improvement. This medication actually doubled survival in patients with advanced disease. We have patients who participated in the trial who are still alive, which is unheard of because the five-year survival rate for pancreatic cancer patients is only 13%-14%. If the drug is approved by the FDA, it will most likely become the new standard of care for advanced pancreatic cancer and could replace chemotherapy as a first-line treatment.

This is a win for the field. Until now, we have been focused on immune therapies that might make tumors more vulnerable to the body's immune system, and on finding new chemotherapy combinations that kill cancer cells. This new treatment has given us a new focus, and I think it will spur a lot of scientific discovery over the next few years. There have only been a handful of KRAS researchers and their relevance to therapy was always questioned. That is about to change. The most important next step for the field is to better understand the biology of cancer. We know that many pancreatic tumors will eventually become resistant to daraxonrasib, and we need to understand how this happens. We also need to identify additional genetic pathways and treatments that can target them. That's how we will turn pancreas cancer from a deadly, deadly cancer into something we can manage-and one day, even cure.

One of the first ways in which this would be really felt by patients is through the repurposing of existing drugs for new diseases. Clearly, even though one could improve the process in a number of ways in terms of speeding up medicinal chemistry programs and potentially speeding up the amount of things such as toxicity trials etc., that is still going to take time. However, if we can take existing drugs, perhaps drugs which have gone off patent or are currently being marketed for another indication, and repurpose them in areas where there are high unmet medical needs, those drugs could go into that new indication in phase 2 in patients and you would know very quickly whether the drug worked or not. Then the route to market or the route to being able to make the drug more broadly available to patients would be much more rapid because you don't have to go through all those earlier stages of toxicity, testing, phase 1 testing, volunteers and so on.

One of the main reasons why compounds fail is that they actually don't work in the patients they are tested in. We may have picked the wrong target since although we've actually created a molecule that, for example, inhibits the activity of the protein in the disease, it may actually turn out that over activity of that e protein isn't as important as we thought it was in that disease. The other reasons molecules fail now is primarily unexpected toxicity. You could take a molecule all the way through to phase 3 trials – the biggest trials in patients – and suddenly find that in your long-term, two-year carcinogenicity studies in animals, that you've got something that is quite cancer-provoking, so you have to stop development. Those are the two reasons: efficacy and toxicity. Somehow, we've got to find a way of trying to increase the chances of success or making the process less costly and leaner.

RAS mutations are one of the most common cancer-causing genetic mutations, and the drug is now being studied in several cancer types. I think it's going to work especially well in tumors that are primarily RAS driven, including colon cancer and lung cancer. It might also work in other cancer types in combination with drugs targeting other genetic mutations, but further research is needed.

I think we're only just scratching the surface at the moment. I think over the next couple of years, we'll start to see some major strides. Obviously, showing the effects on target identification takes some time with new molecules but, certainly, the repositioning effects should be seen in a few years. I think there is great promise in terms of being able to really tap into a much broader chemical space, so we can have a much wider and more varied chemical palette to be able to pick the best molecules for drug discovery from. Also, accelerating the ways in which we can look at the data and glean much more information from it can help us both in terms of patient selection for clinical trials and in terms of being able to pick up signals of efficacy and safety much earlier.

With the current drug discovery paradigm, it takes up to 15 years to translate an idea, such as hypothesizing a certain protein is important in a disease and testing this with targeting the protein with a drug, all the way through to proof of concept. The drug has to be filed with the regulatory authorities, having done all the safety and efficacy testing. It's a long process and it's also very costly. Estimates vary, but it's currently reckoned to cost over 1 billion dollars per drug. That’s partly because you have to pay for all the drugs that didn't make it. By the time you've taken a protein target and you've made a whole load of molecules that affect that target in the way you want them to, you've probably already spent a couple of years on it and then you have to take the best molecule through the appropriate safety testing in animals before proceeding to phase 1 testing in people. Even if you get to phase 1 testing, where you are just giving it to human volunteers for the first time, not even patients, about 95% of the compounds at the stage then fail to make it all the way through to the market. So, you’ve only got a 5% success rate. The odds are not good and, essentially, it is why so many companies have had to merge because, over time, this is becoming less and less sustainable as a business model.

The medication, called daraxonrasib, is the first drug that targets cancer-causing mutations in pancreas cells. The drug targets a mutation in the KRAS gene, part of the RAS genetic family. KRAS mutations are present in 92% of pancreatic cancers. KRAS genes normally act as an "on-off" switch for cell growth. Mutated KRAS genes are stuck in the "on" position and send out a signal that causes cells to divide and grow uncontrollably, allowing cancer to form. Daraxonrasib blocks the KRAS signal by fitting into a keyhole-type spot on the gene. That spot has a complex shape and is difficult to reach within the cell. The drug gets around this problem by using a "passenger protein" as a Trojan horse. When the cell allows this protein in, daraxonrasib tags along.

What we're trying to do here at Benevolent is develop systems and processes that allow us to tap into the huge amount of public information and some propriety databases that we have paid to access and through that, generate hypotheses which our scientists can then triage. We've got over ten times the amount of information in our database at present (and it’s growing) than we believe that companies such as Watson have. Bringing that and filtering the signals from the ‘noise’ to our experienced drug discovery chemists and biologists, means, firstly, we can reduce the amount of time we take to triage new hypotheses, and secondly, we can develop more predictive chemical tools to allow us to make better molecules and also to reposition existing molecules for new indication.

I want us to disrupt the drug discovery and development process and to look at each place on the drug discovery and development pipeline, so that we can be much better at getting the right target, much quicker at getting the right compound and much more confident that those compounds have the right characteristics which mean they will be safe and well tolerated. Then we can go to the right patient population with the right dose, so we would have a much leaner, more successful process and be able to demonstrate the value of our AI technology.

Picking the right target is absolutely fundamental. I mentioned that over half of failures of new medicines in development are due to us picking the wrong target. Even if we just doubled our success rate at picking the right target, it would have a huge impact on the development of new medicines for people. One of the reasons, and why I think artificial intelligence could be really important in helping us do that, is that, quite often, there may be some data buried in the literature that tells us a target is really good. Equally valuable is the fact that there may be something buried in the literature that tells you a target is not good. It's much harder to publish negative data than positive data. That target invalidation can be just as valuable as a target validation. It's really about being able to tap into all that knowledge and look up all the facts. That would mean that our systems and other people's AI systems can really be much more effective at picking the right target.

More specifically, the study showed that the female patient produced very few cathelicidins, which is a natural toxin found in the immune cells of the lungs needed to fight tuberculosis. In most people infected by tuberculosis, tuberculosis bacteria attack the immune cells of the lungs. The immune cells fight the bacteria by eating them. But the tuberculosis bacterium has developed various evasive mechanisms that reduce the immune cells’ ability to digest and thus to kill the Mtb. “You could say that the tuberculosis bacterium has developed a way to lull the immune cells to sleep. This enables the disease the hide inside the immune cells, making it invisible to other parts of the immune system,” Martin Kongsbak-Wismann explains. This is where vitamin D enters the picture. Because vitamin D is able to counteract the soporific effect of the tuberculosis bacteria by making the immune cells produce more of the cathelicidin toxin. “Cathelicidin is like a microscopic needle that is able to pierce the tuberculosis bacteria. And when it does, it weakens the bacteria’s soporific effect on the immune cells. This restores the immune cells’ ability to kill tuberculosis bacteria,” says Martin Kongsbak-Wismann and adds: “We were amazed by the effect of vitamin D. In immune cells from healthy control subjects, vitamin D improved the cells’ ability to fight Mtb, whereas in the female patient’s immune cells we saw no response to vitamin D. This shows that vitamin D is key to the immune system’s ability to fight Mtb and prevent tuberculosis.” Al-Jaberi, F.A.H., et al. (2022) Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor: A case report. Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1038960.

We are now testing the drug in patients with earlier-stage pancreatic cancer, prescribing it while their tumors are still operable and before their cancer spreads.

Carb cycling is an attempt to fine-tune your carbohydrate consumption to alter many aspects of your metabolism. Your plan will include the same protein intake each day but vary carbohydrates according to your activity. Your carb cycling plan may have three low or zero carb days, two moderate carb days, and two high carb days. Meeting your calorie requirements will require including more fats on low-carb days. Carb cycling needs much more planning than a usual calorie-controlled diet. One way is to match your carb cycling to your physical activity. If you go to the gym thrice a week, you could have carbs on those days. The carbs provide energy for your workout, prevent fatigue, and avoid the muscle loss sometimes seen with dieting. The days when you eat little to no carbs force your body to generate energy from other sources, like proteins and fats. But the days when you eat more carbohydrates might reverse this change. You must only eat a high-carb diet on the days you have a heavy workout, which uses up the calories.

The bulk of vitamins and supplements containing fish oil, biotin, and vitamins A, C, and E can potentially promote nail and hair growth. You can find dietary supplements with higher concentrations of vitamins and minerals that aid skin, hair, and nail health. Fish oil supplements make nails and hair shiny. Fish oil also serves as an agent that can decrease signs of aging. If sun exposure damages the skin, the omega-3 fatty acids in fish oil can help. Biotin, also known as B7, increases hair density and strengthens it. It is found naturally in bananas, eggs, and milk. Vitamins are vital for skin health as well. Vitamin A reduces acne flairs and helps with changes due to aging like wrinkling. A vitamin A deficiency may increase the risk of acne because it becomes difficult for dead skin to slough off hair follicles, blocking pores. Vitamin B lowers the risk of precancerous growths and nonmelanoma skin cancer. Vitamin C is an antioxidant. It leads the fight against free radicals to help stimulate collagen and brighten skin. It also helps to prevent the formation of unneeded melanin that causes uneven skin pigmentation.

Biologically, vitamins are absorbed within hours and have instant metabolic effects, such as antioxidants that protect cells or compounds that are building blocks for making hormones. But, many factors impact their efficiency and could keep your body from fully absorbing them. Absorption and effects depend on each individual and what combination of vitamins they take. Gender, age, digestive health, medical conditions, and diet all play a role. One helpful practice to detect deficiencies is to look for the symptoms deficiencies create. Then, look for improvement in your symptoms with supplement intake. You are unlikely to see or feel changes if you do not lack nutrients. If you are chronically tired or see signs of unhealthy nails, hair, or skin, supplements may help as these are indicators that you are lacking nutrients in your diet. If you are unsure, your doctor can order tests to check for deficiencies in your blood.

Your weight loss plan should keep you healthy and strong as you lose the extra weight. Many plans include a diet low in carbohydrates. Carb cycling is a method of optimizing your carbohydrate intake to meet your needs while dieting, fasting, and working out. When you're carb cycling, you consume carbs to meet your needs on some days and avoid them on other days. The aim of carb cycling is to consume carbohydrates when your body needs them and exclude them at other times. Such strategies in your diet plan can help your weight loss efforts. Carbohydrates, or carbs, are a significant part of the average human diet. Along with proteins and fats, they make up the bulk of your daily meals. Most carbohydrates are broken down by your body into glucose to provide energy for your cells and tissues. Carbohydrates in your diet are of three types — sugars, starches, and fiber. Sugars are simple carbs. Glucose, sugar (sucrose), lactose found in milk, and fructose found in fruits, are naturally occurring sugars. Your body metabolizes these molecules rapidly to yield energy. Starches are complex carbs. They're large molecules that consist of hundreds of molecules of simple sugars joined together. Your body needs to break them down to release energy. Starches are found in bread, potatoes, peas, corn, cereals, and pasta. Fiber is also a complex carbohydrate. Human bodies can't break down these large molecules, so they provide no energy. They're usually excreted as they are in the feces. They add bulk to your meal, so you feel full. Fiber in the diet helps avoid constipation and lowers blood sugar and cholesterol levels. Carbohydrates are an essential part of your diet. A typical diet provides 45% to 65% of its calories from carbohydrates. If you have 2,000 calories a day, you should have about 275 grams of carbohydrates. Always try to choose healthy foods for your carb intake:

Daily, if you eat a balanced diet that includes healthy foods, you technically should not need a vitamin supplement. A healthy diet incorporates lean proteins, healthy fats, grains, fruits, and vegetables. But if you do not have a balanced diet, you may be considering hair, skin, and nail vitamins. Some people prefer supplements, sometimes choosing a multivitamin that can supply all of your essential minerals and vitamins. But taking too much of vitamins or unnecessary supplements is wasteful because the body gets rid of excess vitamins and minerals or, worse, it can be dangerous. The following is a guide to choosing which vitamins you may want to consider supplementing and when. Deficiencies in the nutrients that keep the skin, hair, and nails healthy can cause changes over time. For example, not enough intake of vitamins A and E, along with not enough biotin, can cause scaly and rough skin patches, eczema, and hair loss. If there is a deficiency, vitamins will help. However, if there is no deficiency, there is no clear evidence that supplements will make a difference. No research studies concluded that supplements treat or prevent age-related, natural hair damage or loss or lead to healthier skin. Two studies in the early 1990s did suggest that a biotin supplement may cause the hair to become stronger and strengthen weak nails. However, the studies were small and not reproduced.