The woman behind nanoghosts

Prof. Marcelle Machluf of the Technion, who lit one of the 12 torches on Mount Herzl’s Independence Day ceremony, is a promising pioneer in the fight against cancer.

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April 29, 2018 00:56
Prof. Marcelle Machluf

Prof. Marcelle Machluf. (photo credit: Courtesy)

 
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The prestigious journal Nature turned down medical articles written by Prof. Marcelle Machluf – currently dean of the faculty of biotechnology and food engineering at the Technion-Israel Institute of Technology, but it has since relented and published them. The journal Science has refused and not changed its mind, recalls – with an ironic smile – the scientist who specializes in tissue engineering and cancer drug delivery who lit one of the 12 torches at Israel’s 70th Independence anniversary ceremony on Mount Herzl.

“The journals didn’t believe in what I discovered in my research; they said it was ‘too good to be true,’” she said. Her lab studies, which will be tested on patients in the next year or two, have shown that her modified stem cells called nanoghosts can kill every type of solid tumor.

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“We are proud of Prof. Machluf,” said Technion president Prof. Peretz Lavie before the ceremony. “In her achievements, Marcelle is a role model for many generations of students.”

“I thank the State of Israel for this honor,” said Machluf, upon being chosen to for national recognition of her contribution to science and education.

“Every year I look forward to the torch-lighting ceremony, which celebrates the country and its successes. Therefore, there is no greater honor than to be deemed worthy of lighting a torch for the glory of the State of Israel.”

In an interview with The Jerusalem Post a few days before the Mount Herzl event, the 55-year-old scientist said, “I didn’t have a clue about the honor. I don’t know even who recommended me, but I am very proud to have been chosen.” She had never been to the Mount Herzl ceremony before. “I never managed to get tickets.”

In its 70th year, she said, Israel is an “incredible country. I always see the glass as at least half-full, not half-empty. This country is never boring. As in scientific research, not everything can succeed. There is always something to improve. But it has much promise of greatness; in the years ahead, everybody will be jealous of Israel.”

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BORN IN Morocco in 1963, she was brought to Israel as a one-year-old baby by her mother and grandmother after her parents divorced. She grew up in Ashdod; her mother supported the family doing seamstress work and cleaning houses.

After finishing high school and her army service as an aircraft technician, Machluf dreamed of being a physician and applied to medical school, but was not accepted. Instead, she decided to study biology and received a bachelor’s degree in biology from the Hebrew University of Jerusalem, followed by a master’s of science and doctoral degree in biotechnology engineering from Ben-Gurion University of the Negev in Beersheba on liposomes (a tiny, spherical sac of phospholipid molecules enclosing a water droplet for carrying drugs or other substances into the tissues) under the supervision of one of Israel’s biotechnology pioneers, Prof. Smadar Cohen.

For her postdoctoral research, she went to Boston and worked for five years as a fellow at Harvard Medical School and focused on gene therapy, tissue engineering and the control of drug delivery in cancer therapy.

She is married to Yigal, who formerly worked at Motorola and is now a driving teacher. They have three children – Danielle (28), who studies at the Bezalel Institute of Art; Yarden (24), a son studying medicine in Hungary; and Ori, (19), who is serving in the IDF.

Machluf serves as president of the Israel chapter of the Controlled Release Society. She has published over 60 articles in specialized journals that include Nature Biotechnology, Nano Letters and Blood and has written book chapters. Her papers have been cited more than 3,300 times, awarding her an h-index of 30 (Google Scholar). The Technion scientist also has seven patents or patents pending.

Among the prizes the world-renowned researcher has won are the 2004 Alon Award for excellence in science, the 2006 Gutwirth Award for achievements in gene therapy, the 2010 Hershel Rich Technion Innovation Award and the 2014 Juludan Research Prize for outstanding innovative research. She holds an adjunct professor position at the Nanyang Technological University of Singapore.

Her achievements in advanced cancer therapies were acknowledged two years ago by the Science and Technology Ministry in Jerusalem as one of Israel’s 60 most impactful developments and discoveries. The highlights of these achievements appeared in a one-year continuing exhibition at Ben-Gurion International Airport, alongside the works of Nobel Laureates and other renowned Israeli scientists.


MACHLUF BELIEVES that in many cases, nature has found ways and mechanisms to combat most diseases, even though they are not always as effective as humankind would hope. As a biotechnology engineer, she sees her role as identifying such mechanisms and implementing them in safe and efficient biotechnological solutions to better the human condition.

Although she works on cancer daily, she admitted that she is glad she never became an oncologist, “as a cancer specialist has to be very strong to treat patients. It is not for me. Nevertheless, I get lots of mail from patients who ask me for help – but I tell them that unfortunately, our research is not yet at the clinical stage.”

Instead, she works on mice and larger animals such as sheep and pigs specially grown at clinical grade for medical experimentation, which is strictly supervised at the Technion’s Rappaport Faculty of Medicine.

In making the nanoghosts, “We don’t create a new creature; we empty out an adult stem cell from the body so it doesn’t cause the immune system to react. Unlike the Dolly the sheep cloning process, we don’t put in genetic material. It produces an anti-cancer drug, but doesn’t change the biology of the cell.”

Machluf has developed numerous tools for clinical applications using advanced engineering and scientific methods. She has achieved many breakthroughs in the quest to enable more accurate and focused cancer treatment while minimizing effects on healthy cells, using advanced biological technologies.

The nanoghost idea, she continued, began in 2007, aiming to engineer a decoy for the HIV virus.

“My students and I took cells that express markers that the virus usually sticks to. We were told that the cells will wake up the immune system. So we started with stem cells. I suggested in 2009 that we try to do it with cancer. It was a crazy idea, but we got our first results in 2012. The Israel Academy of Sciences and the Humanities provided the initial funding, followed by money for the lab from Edward Satell, a philanthropist from Philadelphia. The patent was approved in the US and Europe in July and soon it will be approved in China and India.”

She and post-doctoral student Tomer Bronstein, who collaborates with her on the research, will set up a company to make and test the discovery.

“We don’t know where we will do Phase-I trials, either in Israel or in Europe, wherever the US Food and Drug Administration approves them. I prefer that they are all in Israel.” The nanoghosts, said Machluf, work on all solid cancers – which are 90% of all malignant tumors – “even in the brain, because they pass over the blood-brain barrier. We haven’t yet tried liquid cancers, such as leukemia and lymphoma, but they may work on them as well. You can’t try it on any type of tumor, because it costs $300,000 or $400,000 to try each out. But in lab animals, it fought small lung carcinoma, glioma, breast cancer, prostate and pancreatic cancer.”

I don’t know if this is the answer for all cancer in humans, as it is a difficult fight because it always changes. But we hope our discovery will be the answer to replace many cancer drugs. It’s hard for cancer drugs to get inside tumors, so they usually don’t cure. But with our technology, they will be more accessible.”

Machluf noted that she always worked in slow-release drugs for cancer, but they were synthetic and not biological.”

Asked about various unproven “cancer cures” that appear on the Internet, such as the spice curcumin, she said it “has advantages; there are articles that claim that if one takes it in very concentrated form, it can affect cancer. But it has not been proven to do the job. It gives false hopes. Many people try to take advantage of desperate patients. I hope cancer patients don’t depend on such claims and get conventional anti-cancer treatment too late. I believe that one has to combine lifestyle changes with conventional treatment.


BEING A woman scientist is never easy, admits Machluf. One’s family and career often clash and compete for her time. Today, she has a large lab with 25 master’s, doctoral and postdoctoral students, many of them women.”

Asked if, having been born in Casablanca, she observed any discrimination against Sephardim, Machluf said there was, but fortunately she did not suffer any personally.

“There are male cliques in science, but over time, they can’t ignore our talents. But I got inspiration from Smadar Cohen, who I worked under at BGU. She pushed me a lot. And my husband helped so much when the children were small. He came with me to the US when I did my post-doctoral work. My mother also came to the US to help out.”

Her lab will soon have an ultra-Orthodox Jewish man who will join her lab as a doctoral student.

“He has four children and is brilliant. He studied engineering and pharmaceutical science. His wife is doing a doctorate at Tel Aviv University in philosophy.”

She worries about the brain drain.

“We compete with other scientific institutions abroad. We have smart, capable people, and there aren’t enough good jobs here for them. It’s sad, as they are our natural resource.”

She praised Prof. Peretz Lavie, the Technion’s president, who is actually a psychologist who specialized in sleep science. “He is a man with vision,” she concluded.

To be a scientist, she says, one needs to have a lot of motivation, curiosity and patience.

“It is nonstop. You don’t go home at 4 p.m. and put your work aside. When at home, you read, learn, try to know what others are doing. There is also a lot of competition.”

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