{"id":1113,"date":"2022-07-22T12:40:14","date_gmt":"2022-07-22T12:40:14","guid":{"rendered":"https:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=1113"},"modified":"2022-07-22T12:40:14","modified_gmt":"2022-07-22T12:40:14","slug":"what-is-in-e5-harold-katchers-patent","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2022\/07\/22\/what-is-in-e5-harold-katchers-patent\/","title":{"rendered":"What is in E5? Harold Katcher’s patent"},"content":{"rendered":"

Harold Katcher\u2019s patent was unveiled last week, and it\u2019s not what I thought it would be.<\/span><\/p>\n

I thought it would be a list of several molecular forms, together with recipes for how to make them and how to administer them intravenously for increased longevity.\u00a0<\/span><\/p>\n

I hoped it would inspire laboratories around the world to replicate Harold\u2019s results and to vary the formula with the intent of optimizing results and streamlining delivery. I imagined a quantum advance in parabiosis-derived experimentation.\u00a0<\/span><\/p>\n

Instead, the patent seeks to cover a broad range of techniques for extracting proteins and entire exosomes from blood plasma. It may be designed to obfuscate. I am unfamiliar with patent law, and this may be entirely conventional; instead of giving explicit instructions that another researcher can follow, there are several alternatives at every step, with the claim that they are all variations on the basic technique, and the patent covers them all. I presume that Harold knows which of these options at each step are the ones used to create E5; but no one reading the patent could recreate Harold\u2019s work without some inspired guesses.<\/span><\/p>\n

Background<\/b><\/p>\n

Ever since the Stanford parabiosis experiments of 2005, there has been evidence that aging is centrally coordinated and that the blood transmits information telling the body how old it is. Young tissues quickly deteriorate when exposed to the blood plasma of an old animal, and old tissues are rejuvenated in the presence of young blood plasma.<\/span><\/p>\n

So the pressing question is: what is it in the plasma that transmits these signals? Is it predominantly <\/span>pro-aging signals<\/span><\/a> that need to be removed, or predominantly <\/span>anti-aging signals<\/span><\/a> that need to be enhanced? How many such chemicals are there? Are they proteins or active RNAs or something else?<\/span><\/p>\n

These are difficult questions because blood plasma contains thousands of molecular signals in trace amounts. The quantities vary with activity and time of day, and many of them vary with age. We would dearly love to have a recipe for a handful of transcription factors that need to be added or removed, with the result that they would trigger readjustments in the rest.\u00a0<\/span><\/p>\n

I had assumed until last week that Harold has this information, and that he has held it back from the public while his business partner secures patent rights and builds a distribution network for humans.\u00a0<\/span><\/p>\n

But now it seems that Harold has general knowledge of the class of chemicals signals that is most effective, but that he does not know specific molecular formulas. Indication is that it is a class of proteins.\u00a0<\/span><\/p>\n

Harold has told us that he has been building facilities for synthesizing E5. The patent seems to say that he has some techniques for extracting from plasma a cocktail of many substances that remain incompletely characterized. Akshay has told me that they get plasma from pig\u2019s blood, discarded by butchers.<\/span><\/p>\n

There are large proteins and short peptides and everything in between. A “plasma fraction” may contain a specific range of molecular weights. But in the patent, several different ranges are listed, so we don’t have the crucial information, “which range is the effective one?” I presume that Harold knows.<\/span><\/p>\n

Perhaps among readers of this blog there are people well-versed in biotech patent law and others who know more about the biochemistry of blood-derived proteins. If so, please contact me and respond to this patent from a more informed perspective than i can derive.<\/span><\/p>\n

Imperative for the near future<\/b><\/p>\n

We know that the active ingredients are proteins, and Harold knows the range of molecular weights. Several different ranges are listed in the patent, and several fractioning techniques are specified for specifying them. I presume that one of these leads to successful rejuvenation and the others are decoys.\u00a0<\/span><\/p>\n

So, the next step will require Harold\u2019s cooperation, because even after publication of the patent, no one else will be able to replicate his formula. If he and Akshay are willing to subject E5 to laboratory analysis, then the protein constituents can be individually characterized. I personally don\u2019t know how this is done, but I do know it is possible because biochemists generate pictures like this one routinely.<\/span><\/p>\n

\"\"<\/p>\n

The number of chemicals in a given range of molecular weights is probably small, perhaps a few dozen; and of these, the active ingredients necessary for the formula to work constitute a smaller set, perhaps less than a dozen. Once we have the chemical formulas for all the constituents of E5, we can test different combinations of them and within a year of trial and error, we should be able to identify the minimal effective set. Then these can be synthesized in a modern factory and we won\u2019t need a river of pig\u2019s blood to rejuvenate humanity.<\/span><\/p>\n

Harold is not the only or even the first to conduct research with blood-derived proteins inspired by parabiosis experiments. There is ongoing research at Stanford, Berkeley, Harvard, Alkahest and now Altos Labs.\u00a0<\/span><\/p>\n

The next steps are crucial, and they will require more investment than Harold and Akshay’s Yuvan Research<\/a> has available. I hope Yuvan will partner with a laboratory that has resources to analyze E5 and then test constituent ingredients to optimize rejuvenation effects with a minimal set of injected proteins.<\/p>\n","protected":false},"excerpt":{"rendered":"

Harold Katcher\u2019s patent was unveiled last week, and it\u2019s not what I thought it would be. I thought it would be a list of several molecular forms, together with recipes for how to make them and how to administer them intravenously for increased longevity.\u00a0 I hoped it would inspire laboratories around the world to replicate … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":1114,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1113","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"yoast_head":"\nWhat is in E5? 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\/\/mathforum.org\/~josh","sameAs":["http:\/\/AgingAdvice.org"],"url":"https:\/\/scienceblog.com\/joshmitteldorf\/author\/joshmitteldorf\/"}]}},"jetpack_featured_media_url":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2022\/07\/3d-protein-structure.png","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-hX","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/1113","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=1113"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/1113\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media\/1114"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=1113"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=1113"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=1113"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}