나는 아직도 기억하고 있다. 어렸을적 시골에서 벼심기를 할때쯤이면, 뱀도 출몰하여, 겨울내 Hibernation하다 뛰쳐나오면 배가 고파 닥치는데로 물어뜯는 독사들에게 많은, 당시의 농부 아저씨들이 주로 발 아니면 장단지를 물려 고생을 했었던 장면을 여러번 봤던 기억이 있고, 심한 경우에는 다리를 절단하는 경우까지 봤던 기억이 있다.
물고 도망가는 뱀을 쫒아가 나뭇가지, 또는 농기구를 사용하여 뱀의 숨을 끊었던, 당시 농부 어른들이 복수를 했었던, 이기사를 읽으면서 아스라히 70여년 전의 기억을 떠올리게했다. 그때의 무서운 기억때문에 평생을 통해서 뱀을 보면, 자연적으로 몸이 움추러 들곤한다.
만약에 당신이 재수없게 뱀에게 물려 독액이 몸속으로 스며들면, 빅토리아 시대빼부터 사용해 왔던 해독제를 사용해 보는게 가장 적절한 방법으로 머리에 떠 올릴것이다. 뱀의 송곳이에서 추출한 독액을 말이나 또는 다른 동물들에게 소량주입해서 면역체계의 반응을 살핀후, 동물의 피를 추출하여 독액에 대항하여 싸우는 항생체를 얻기위해 깨끗하게 정화시켜 사용한다.
이방법으로 해독하기위해서 많은 시행착오가 있었고, 때로는 매우 위험함이 함께 한다. 그러나 그러한 반대적 상황에 대해서는 별로 많이 알려진게 없이 일종의 민간 치료법으로 오늘까지 이어져 왔다고 할수있겠다.
전문가들은 뱀에게 물렸을때 더 낳은 방법으로 치료하기위해 더좋은 방법을 찾는데 많은 시간을 보냈었다. 희생자가 많을때는 하루에 200명정도가 뱀에 물려 목숨을 잃었었다.
마침내 과학자들은 오랫동안 이분야 연구에서 제외 됐었던 줄기세포연구로 게놈지도를 만드는데 성공한 것이다. 과학자들은 해독제를 생산하여 뱀에 물인 환자에 적용시켜, 21세기에도 일년에 수천명, 아니면 수만명씩 희생되는 재앙을 막을수 있기를 희망하고 있다.
인도의 과학자들이 이와 병행해서, 인도에서 가장 무서운 4종류의 뱀들중 하나인 인도코브라에 물려 (50,000 snakebite deaths India sees a year.) 목숨을 잃는 희생자가 자그만치 50,000명 이상인데, 인도코브라의 게놈을 일렬로 배열하는데 성공한 것이다.
현재 지구상에서는 매 5분마다 뱀에 물려 희생당하는 숫자가 50명이라고 한다.
Hubrecht협회에서 생명공학과 줄기세포연구의 최고 조사관, Hans
Clevers씨는 그의 연구실에서 만든, 뱀의 Fang에서 추출한 독액과 똑같은 물질이, 해독제로 사용되리라고는 한번도 생각해 본적이 없었다고 실토했다.
약 10여년전에 그는 인간의 오가노이드를 만들수있는 기술을 발명 했었다(technique to make human organoids). 즉 환자들로 부터 추출한 줄기세포를 이용하여 미니 장기들을 만들었던 것이다. 그들은 닥터들이, 혁명적이고, 암치료 같은 극히 개인적으로 인체밖에서 drugs를 특별히 이용한 실험의 효과를 실험 할수있도록 허락 했었다.
뱀의 Fang에서 나오는 독액은 고혈압과 협심증을 갖인 우리 인간들을 치료하는데 꼭 필요한 약품을 제조하는데 사용되여 왔었다(Snake venom has been used to make drugs).
"뱀의 Fang 나오는 독액은 매우 무섭고 혐오스러움을 느끼게 하지만, 놀랄정도로 매우 유용하게 쓰인다"라고 Seshagari씨는 설명까지 덧부친다.
(CNN)If you're unlucky enough to have a poisonous snake sink its fangs into you, your best hope is an antivenom, which has been made in the same way since Victorian times.
It involves milking snake venom by hand and injecting it into horses or other animals in small doses to evoke an immune response. The animal's blood is drawn and purified to obtain antibodies that act against the venom.
Producing antivenom in this way can get messy, not to mention dangerous. The process is error prone, laborious and the finished serum can result in serious side effects.
Experts have long called for better ways to treat snake bites, which kill some 200 people a day.
Now -- finally -- scientists are applying stem cell research and genome mapping to this long-ignored field of research. They hope it will bring antivenom production into the 21st Century and ultimately save thousands, if not hundreds of thousands, of lives each year.
Researchers in the Netherlands have created venom-producing glands from the Cape Coral Snake and eight other snake species in the lab, using stem cells. The toxins produced by the miniature 3-D replicas of snake glands are all but identical to the snake's venom, the team announced Thursday.
In a parallel breakthrough, scientists in India have sequenced the genome of the Indian cobra, one of the country's "big four" snakes that are responsible for most of the 50,000 snakebite deaths India sees a year.
From cancer to snake venom
Hans Clevers, the principal investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, never expected to be using his lab to make snake venom.
A decade ago, he invented the technique to make human organoids -- miniature organs made from the stem cells of individual patients. They've allowed doctors to test the specific effects of drugs safely outside the body, something that has revolutionized and personalized areas such as cancer treatment.
The scientists have reproduced the venom gland of the Cape coral snake, seen here in the Olomouc Zoo, Czech Republic, on May 11, 2018.
So why did he decide to culture a snake venom gland?
Clevers said it was essentially a whim of three PhD students working in his lab who'd grown bored of reproducing mouse and human kidneys, livers and guts. "I think they sat down and asked themselves what is the most iconic animal we can culture? Not human or mouse. They said it's got to be the snake. The snake venom gland."
"They assumed that snakes would have stem cells the same way mice and humans have stems cells but nobody had ever investigated this," said Clevers.
After sourcing some fertilized snake eggs from a dealer, the researchers found they were able to take a tiny chunk of snake tissue, containing stem cells, and nurture it in a dish with the same growth factor they used for human organoids -- albeit at a lower temperature -- to create the venom glands. And they found that these snake organoids -- tiny balls just one millimeter wide -- produced the same toxins as the snake venom.
The snake venom gland organoids as seen under a microscope./
"Open them up and you have a lot of venom. As far as we can tell, it's identical. We've compared it directly to the venom from the same species of snake and we find the exact same components," said Clevers, who was an author of the paper that published in the journal Cell last week.
The team compared their lab-made venom with the real thing at the genetic level and in terms of function, finding that muscle cells stopped firing when exposed to their synthetic venom.
Cells and DNA, not horses
The current antivenoms available to us, produced in horses not humans, trigger relatively high rates of adverse reactions, which can be mild, like rash and itch, or more serious, like anaphylaxis. It's also expensive stuff. Wellcome estimate that one vial of antivenom costs $160, and a full course usually requires multiple vials.
Even if the people who need it can afford it -- most snakebite victims live in rural Asia and Africa -- the world has less than half of the antivenom stock it needs, according to Wellcome. Plus antivenoms have been developed for only around 60% of the world's venomous snakes.
In this context, the new research could have far-reaching consequences, allowing scientists to create a biobank of snake gland organoids from the 600 or so venomous snake species that could be used to produce limitless amounts of snake venom in a lab, said Clevers.
"The next step is to take all that knowledge and start investigating new antivenoms that take a more molecular approach," said Clevers.
To create an antivenom, genetic information and organoid technology could be used to make the specific venom components that cause the most harm -- and from them produce monoclonal antibodies, which mimic the body's immune system, to fight the venom, a method already used in immunotherapy treatments for cancer and other diseases.
"It's a great new way to work with venom in terms of developing new treatments and developing antivenom. Snakes are very difficult to look after," Cammack said, who was not involved with the research.
Clevers said his lab now plans to make venom gland organoids from the world's 50 most venomous animals and they will share this biobank with researchers worldwide. At the moment, Clevers said they are able to produce the organoids at a rate of one a week.
But producing antivenom is not an area that pharmaceutical companies have traditionally been keen to invest in, Clevers said
Campaigners often describe snakebites as a hidden health crisis, with snakebites killing more people than prostrate cancer and cholera worldwide, Cammack said.
"There's no money in the countries that suffer. Don't underestimate how many people die. Sharks kill about 20 per year. Snakes kill 100,000 or 150,000," said Clevers.
"I'm a cancer researcher essentially and I am appalled by the difference in investment in cancer research and this research."
Venom is a complex cocktail
One challenge to making synthetic antivenom is the sheer complexity of how a snake disables its prey. Its venom contains several different components that have different effects.
Researchers in India have sequenced the genome of the Indian Cobra, in an attempt to decode the venom.
Published in the journal Nature Genetics earlier this month, it's the most complete snake genome assembled and contains the genetic recipe for the snake venom, establishing the link between the snake's toxins and the genes that encode them. It's not a straightforward cocktail -- the team identified 19 genes out of 139 toxin genes as the ones responsible for causing harm in humans.
"It's the first time a very medically important snake has been mapped in such detail," said Somasekar Seshagiri, president of SciGenom Research Foundation, a nonprofit research center in India.
"It creates the blueprint of the snake and helps us get the information from the venom glands." Next, his team will map the genomes of the saw-scaled viper, the common krait and the Russell's viper -- the rest of India's "big four." This could help make antivenom from the glands as it will be easier to identify the right proteins.
In tandem, both breakthroughs will also make it easier to discover whether some of the potent molecules contained in snake venom are themselves worth prospecting as drugs -- allowing snakes to make their mark on human health in a different way to how nature intended -- by saving lives.
Snake venom has been used to make drugs that treat hypertension (abnormally high blood pressure) and heart conditions such as angina.
"As well as being scary, venom is amazingly useful," Seshagari said.
https://www.cnn.com/2020/01/29/health/snake-venom-lab-organoids-stem-cell-scn/index.html
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